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Cochrane Database of Systematic Reviews
Nutrition-specific interventions for preventing and controlling

anaemia throughout the life cycle: an overview of systematic
reviews (Review)
da Silva Lopes K, Yamaji N, Rahman MO, Suto M, Takemoto Y, Garcia-Casal MN, Ota E
da Silva Lopes K, Yamaji N, Rahman MO, Suto M, Takemoto Y, Garcia-Casal MN, Ota E.
Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of systematic
reviews.
Cochrane Database of Systematic Reviews 2021, Issue 9. Art. No.: CD013092.
DOI: 10.1002/14651858.CD013092.pub2.
www.cochranelibrary.com
Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of
systematic reviews (Review)
Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews
TABLE OF CONTENTS
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
BACKGROUND.............................................................................................................................................................................................. 5
OBJECTIVES.................................................................................................................................................................................................. 8
METHODS..................................................................................................................................................................................................... 8
RESULTS........................................................................................................................................................................................................ 11
Figure 1.................................................................................................................................................................................................. 12
DISCUSSION.................................................................................................................................................................................................. 33
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 38
ACKNOWLEDGEMENTS................................................................................................................................................................................ 38
REFERENCES................................................................................................................................................................................................ 40
ADDITIONAL TABLES.................................................................................................................................................................................... 54
APPENDICES................................................................................................................................................................................................. 183
WHAT'S NEW................................................................................................................................................................................................. 191
HISTORY........................................................................................................................................................................................................ 191
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 191
DECLARATIONS OF INTEREST..................................................................................................................................................................... 191
SOURCES OF SUPPORT............................................................................................................................................................................... 192
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 192
NOTES........................................................................................................................................................................................................... 192
INDEX TERMS............................................................................................................................................................................................... 192
Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of systematic reviews i
(Review)
Informed decisions.
[Overview of Reviews]
Nutrition-specific interventions for preventing and controlling anaemia

throughout the life cycle: an overview of systematic reviews
Katharina da Silva Lopes1, Noyuri Yamaji2, Md. Obaidur Rahman2, Maiko Suto3, Yo Takemoto4, Maria Nieves Garcia-Casal5, Erika Ota2
1Graduate School of Public Health, St. Luke's International University, Tokyo, Japan. 2Global Health Nursing, Graduate School of
Nursing Science, St. Luke's International University, Tokyo, Japan. 3Department of Health Policy, National Center for Child Health and
Development, Tokyo, Japan. 4Department of Obstetrics and Gynaecology, School of Medicine, Juntendo University, Tokyo, Japan.
5Department of Nutrition and Food Safety, World Health Organization, Geneva, Switzerland
Contact: Erika Ota, ota@slcn.ac.jp.
Editorial group: Cochrane Developmental, Psychosocial and Learning Problems Group.

Publication status and date: Edited (no change to conclusions), published in Issue 1, 2022.
Citation: da Silva Lopes K, Yamaji N, Rahman MO, Suto M, Takemoto Y, Garcia-Casal MN, Ota E. Nutrition-specific interventions for
preventing and controlling anaemia throughout the life cycle: an overview of systematic reviews. Cochrane Database of Systematic
Reviews 2021, Issue 9. Art. No.: CD013092. DOI: 10.1002/14651858.CD013092.pub2.
ABSTRACT
Background
Anaemia is a prevalent health problem worldwide. Some types are preventable or controllable with iron supplementation (pills or drops),
fortification (sprinkles or powders containing iron added to food) or improvements to dietary diversity and quality (e.g. education or
counselling).
Objectives
To summarise the evidence from systematic reviews regarding the benefits or harms of nutrition-specific interventions for preventing and
controlling anaemia in anaemic or non-anaemic, apparently healthy populations throughout the life cycle.
Methods
In August 2020, we searched MEDLINE, Embase and 10 other databases for systematic reviews of randomised controlled trials (RCTs) in
anaemic or non-anaemic, apparently healthy populations. We followed Cochrane methodology, extracting GRADE ratings where provided.
The primary outcomes were haemoglobin (Hb) concentration, anaemia, and iron deficiency anaemia (IDA); secondary outcomes were iron
deficiency (ID), severe anaemia and adverse effects (e.g. diarrhoea, vomiting).
Main results
We included 75 systematic reviews, 33 of which provided GRADE assessments; these varied between high and very low.
Infants (6 to 23 months; 13 reviews)
Iron supplementation increased Hb levels and reduced the risk of anaemia and IDA in two reviews. Iron fortification of milk or cereals,
multiple-micronutrient powder (MMNP), home fortification of complementary foods, and supplementary feeding increased Hb levels and
reduced the risk of anaemia in six reviews. In one review, lipid-based nutrient supplementation (LNS) reduced the risk of anaemia. In
another, caterpillar cereal increased Hb levels and reduced IDA prevalence. Food-based strategies (red meat and fortified cow's milk, beef)
showed no evidence of a difference (1 review).
Preschool and school-aged children (2 to 10 years; 8 reviews)
Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of systematic reviews 1
(Review)
Informed decisions.
Daily or intermittent iron supplementation increased Hb levels and reduced the risk of anaemia and ID in two reviews. One review found
no evidence of difference in Hb levels, but an increased risk of anaemia and ID for the intermittent regime. All suggested that zinc plus iron
supplementation versus zinc alone, multiple-micronutrient (MMN)-fortified beverage versus control, and point-of-use fortification of food
with iron-containing micronutrient powder (MNP) versus placebo or no intervention may increase Hb levels and reduce the risk of anaemia
and ID. Fortified dairy products and cereal food showed no evidence of a difference on the incidence of anaemia (1 review).
Adolescent children (11 to 18 years; 4 reviews)
Compared with no supplementation or placebo, five types of iron supplementation may increase Hb levels and reduce the risk of anaemia
(3 reviews). One review on prevention found no evidence of a difference in anaemia incidence on iron supplementation with or without folic
acid, but Hb levels increased. Another suggested that nutritional supplementation and counselling reduced IDA. One review comparing
MMN fortification with no fortification observed no evidence of a difference in Hb levels.
Non-pregnant women of reproductive age (19 to 49 years; 5 reviews)
Two reviews suggested that iron therapy (oral, intravenous (IV), intramuscular (IM)) increased Hb levels; one showed that iron folic acid
supplementation reduced anaemia incidence; and another that daily iron supplementation with or without folic acid or vitamin C increased
Hb levels and reduced the risk of anaemia and ID. No review reported interventions related to fortification or dietary diversity and quality.
Pregnant women of reproductive age (15 to 49 years; 23 reviews)
One review apiece suggested that: daily iron supplementation with or without folic acid increased Hb levels in the third trimester or at
delivery and in the postpartum period, and reduced the risk of anaemia, IDA and ID in the third trimester or at delivery; intermittent iron
supplementation had no effect on Hb levels and IDA, but increased the risk of anaemia at or near term and ID, and reduced the risk of side
effects; vitamin A supplementation alone versus placebo, no intervention or other micronutrient might increase maternal Hb levels and
reduce the risk of maternal anaemia; MMN with iron and folic acid versus placebo reduced the risk of anaemia; supplementation with oral
bovine lactoferrin versus oral ferrous iron preparations increased Hb levels and reduced gastrointestinal side effects; MNP for point-of-use
fortification of food versus iron and folic acid supplementation might decrease Hb levels at 32 weeks' gestation and increase the risk of
anaemia; and LNS versus iron or folic acid and MMN increased the risk of anaemia.
Mixed population (all ages; 22 reviews)
Iron supplementation versus placebo or control increased Hb levels in healthy children, adults, and elderly people (4 reviews). Hb levels
appeared to increase and risk of anaemia and ID decrease in two reviews investigating MMN fortification versus placebo or no treatment,
iron fortified flour versus control, double fortified salt versus iodine only fortified salt, and rice fortification with iron alone or in combination
with other micronutrients versus unfortified rice or no intervention. Each review suggested that fortified versus non-fortified condiments
or noodles, fortified (sodium iron ethylenediaminetetraacetate; NaFeEDTA) versus non-fortified soy sauce, and double-fortified salt versus
control salt may increase Hb concentration and reduce the risk of anaemia. One review indicated that Hb levels increased for children
who were anaemic or had IDA and received iron supplementation, and decreased for those who received dietary interventions. Another
assessed the effects of foods prepared in iron pots, and found higher Hb levels in children with low-risk malaria status in two trials, but no
difference when comparing food prepared in non-cast iron pots in a high-risk malaria endemicity mixed population.
There was no evidence of a difference for adverse effects. Anaemia and malaria prevalence were rarely reported. No review focused on
women aged 50 to 65 years plus or men (19 to 65 years plus).
Authors' conclusions
Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool
and school-aged children and pregnant and non-pregnant women. Iron fortification of foods in infants and use of iron pots with children
may have prophylactic benefits for malaria endemicity low-risk populations. In any age group, only a limited number of reviews assessed
interventions to improve dietary diversity and quality. Future trials should assess the effects of these types of interventions, and consider
the requirements of different populations.
PLAIN LANGUAGE SUMMARY
Interventions throughout life for the prevention or treatment of anaemia
What is the issue?
Anaemia (low iron levels in the blood) is a health problem worldwide, caused by nutritional (e.g. nutrient deficiencies) or non-nutritional
(e.g. diseases or genetic disorders) factors. Its health consequences include fatigue, loss of productivity and adverse pregnancy and child
outcomes.
Why is this important?
(Review)
Informed decisions.
Iron deficiency (ID) is a common cause of nutritional anaemia, resulting from a lack of iron in the diet or reduced absorption of iron in
the body (e.g. components in coffee, tea or cocoa inhibit iron absorption, while beverages and foods high in vitamin C, such as fruits and
vegetables, enhance iron absorption). Some types of anaemia are preventable or controllable with iron supplementation (via capsules or
drops), fortification (food enriched with sprinkles or powders containing iron) or improvements to diet diversity and quality (e.g. education
or counselling).
What evidence did we find?
Infants (6 to 23 months)
Two reviews suggested that iron supplementation increased haemoglobin (Hb) levels, and reduced the risk of anaemia and iron deficiency
anaemia (IDA) compared with placebo, no intervention or other interventions. Six reviews suggested that iron fortification of milk or
cereals, multiple-micronutrient powder (MMNP), home fortification of complementary foods and supplementary feeding increased Hb
levels and reduced the risk of anaemia. In one review apiece, lipid-based nutrient supplementation (LNS) reduced the risk of anaemia,
while caterpillar cereal increased Hb levels and reduced IDA prevalence.
Preschool and school-aged children (2 to 10 years)
Two reviews suggested that daily or intermittent (e.g. 1 to 3 times per week) iron supplementation increased Hb levels and reduced the
risk of anaemia and ID. For daily versus intermittent iron supplementation, one review found no difference in Hb levels, but an increased
risk of anaemia and ID for the intermittent regime. One review apiece found higher Hb levels and reduced risk of anaemia and ID for zinc
plus iron supplementation versus zinc alone, multiple-micronutrient (MMN)-fortified beverages, and point-of-use fortification of food with
iron-containing micronutrient powder (MNP).
Adolescent children (11 to 18 years)
Three reviews for prevention or treatment suggested that intermittent iron supplementation alone or in combination with other
micronutrients, iron supplementation with or without folic acid supplementation, or other micronutrient supplementation increased Hb
levels and reduced the risk of anaemia. One review suggested that nutritional supplementation and counselling reduced IDA. In one review
for prevention, iron supplementation with or without folic acid appeared to increase Hb levels but have no effect on the incidence of
anaemia.
Non-pregnant women of reproductive age (19 to 49 years)
Two reviews suggested that iron therapy (oral, intravenous, intramuscular) increased Hb levels. One review found that intravenous iron
increased Hb levels compared with oral iron, and another that daily iron supplementation with or without folic acid or vitamin C increased
Hb levels and reduced the risk of anaemia and ID.
Pregnant women of reproductive age (15 to 49 years)
In one review, daily iron supplementation with or without folic acid increased Hb levels in the third trimester or at delivery, and in
the postpartum period, and reduced the risk of anaemia, IDA and ID in the third trimester or at delivery. Six reviews suggested that
intravenous iron versus oral iron or intramuscular iron increased Hb levels. In one review, vitamin A supplementation alone versus placebo,
no intervention or other micronutrient increased Hb levels and reduced the risk of anaemia for the mother. One review found that
supplementation with oral bovine lactoferrin versus oral ferrous iron preparations increased Hb levels and reduced gastrointestinal side
effects. In one review, compared to iron or folic acid and MMNs, LNS increased the risk of anaemia.
Mixed population (all ages)
Iron supplementation versus placebo or control increased Hb levels in healthy children, adults, and elderly people in four reviews. In two
reviews, MMN fortification versus placebo or no treatment increased Hb levels in children, as did iron supplementation, but Hb levels
decreased for those receiving dietary interventions. Intravenous iron resulted in higher Hb levels than oral iron in one review. In another,
vitamin B12 or folic acid supplementation did not increase Hb levels. Each review suggested that iron fortification of food, iron-fortified soy
sauce, double-fortified salt with iron and iodine, and fortified condiments or noodles increased Hb levels and reduced the risk of anaemia.
In one review, foods prepared in iron pots showed the potential to increase Hb levels in children.
No review focused on older adult women (50 to 65 years plus) or men (19 to 65 years plus), and anaemia and malaria prevalence were
rarely reported.
What does this mean?
Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool
and school-aged children and pregnant and non-pregnant women. Iron fortification of foods in infants and use of iron pots with children
may have benefits for low-risk populations. Many trials reported the effects of supplementations, but very few reviews focused on
(Review)
Informed decisions.
fortification or improving diet diversity and quality. Future trials should focus on different types of interventions to increase food variety
and dietary quality.
(Review)
Informed decisions.
BACKGROUND respectively (WHO 2015). Anaemia prevalence decreased globally

from 33% to 29% in non-pregnant women, from 43% to 38% in
Description of the condition pregnant women, and from 47% to 43% in children between 1995
and 2011 (Stevens 2013). Other studies reported that between 1993
Anaemia is defined as a decreased level of red blood cells,
and 2013, the global prevalence of anaemia improved by only
abnormal red blood cell morphology, or an inadequate amount
0.2% to 0.3% points (Kassebaum 2014; Mason 2013). This slow
of haemoglobin in red blood cells which, consequently, leads
progress, coupled with the overall burden of anaemia, has lead
to an insufficient supply of oxygen in the body. It results from
to anaemia's inclusion in the global nutrition targets to improve
decreased red blood cell production (erythropoiesis), increased
maternal, infant, and child nutrition agreed by the World Health
destruction, blood loss, or a combination of these factors. The
Assembly in 2012 (WHO 2014a); the second of the six global goals
underlying cause of anaemia (e.g. nutritional deficiencies, diseases,
aims for a 50% reduction of anaemia in women of reproductive age
or genetic disorders) is frequently used to classify anaemia into
by 2015 (WHO 2014b). In addition, anaemia is indirectly included
nutritional and non-nutritional anaemia (WHO 2017). Causes and
in the Sustainable Development Goals (SDGs); according to the
treatment of non-nutritional anaemia have been discussed in
second goal on ending hunger, target 2.2 aims to end all forms of
other Cochrane Reviews (Fortin 2018; Gordon 2021; Siegfried 2012).
malnutrition by 2030, by addressing, in particular, the nutritional
One of the most common causes of anaemia is iron deficiency
needs of children under five years of age, adolescent girls, pregnant
(ID), which is estimated to account for approximately 50% of
and lactating women, and older people (UN 2015).
all anaemia cases (Stevens 2013; Stoltzfus 2004). However, more
recent estimates suggest that anaemia due to ID accounts for Blood haemoglobin (Hb) concentration is most commonly used as
less than 50%, depending on the country-specific context (Petry an indicator of anaemia, since it is relatively easy and inexpensive
2016a). Anaemia of chronic disease, another common type of to measure. Whilst it alone cannot determine the underlying
anaemia, is multifactorial and its diagnosis generally requires cause of anaemia, in combination with other measurements,
the presence of chronic inflammation (i.e. infection, autoimmune Hb concentration can provide important information about the
disease, kidney disease, or cancer) (Weiss 2005). Numerous other severity of ID (WHO/CDC 2007). Blood Hb concentration levels
nutritional and non-nutritional factors, in combination or isolation, currently used by the WHO to define anaemia are: less than 110 g/L
have been associated with anaemia, such as vitamin deficiencies for children under five years of age and pregnant women; less than
(including folate, vitamin B12, and vitamin A), inflammation, 115 g/L for children aged 5 to 11 years; 120 g/L for children aged
infectious diseases (i.e. malaria; soil-transmitted helminthiasis, 12 to 14 years and non-pregnant women; and less than 130 g/L for
especially hookworm infection; HIV; cancer; and tuberculosis), as men (WHO 2011). In this overview of reviews, we use the anaemia
well as genetic or acquired impairment of haemoglobin synthesis, cut-offs defined by the WHO to summarise the benefits or harms
and production and survival of red blood cells (Camaschella of nutrition-specific interventions for preventing and controlling
2015; Lopez 2016). In the state of infection or inflammation, anaemia throughout the life cycle.
iron absorption is decreased as an innate immune response to
restrict iron availability for pathogens (Hurrell 2012). Anaemia may Description of the interventions
also be the result of physiological or pathophysiological acute or
The reasons for anaemia development are diverse, but poor
chronic blood losses. In menstruating women and adolescent girls,
nutrition is one of its main causes (WHO 2017). ID is a common
periods are the most common cause of iron deficiency anaemia
nutritional deficiency worldwide and jointly responsible for the
(IDA), which, in some cases, may be excessive (i.e. menorrhagia,
high and persistent prevalence of anaemia. However, various other
metrorrhagia) (WHO/CDC 2008). In men and post-menopausal
micronutrients may be lacking in inadequate and imbalanced diets
women, bleeding in the gastrointestinal tract may be a common
and contribute to micronutrient deficiencies and the emergence
cause of anaemia (Lopez 2016). The health consequences of
of anaemia (WHO 2015; WHO 2017). Micronutrient deficiencies,
anaemia include fatigue during the early stages of the disease,
alone or in combination, manifest when requirements cannot
coupled with a negative effect on productivity due to weakness,
be satisfied through adequate provision, intake, or absorption
loss of energy, and dizziness; such loss of productivity also
of nutrients. To counter nutritional anaemia, several different
has an important impact on social and economic development
approaches for dietary improvement have been implemented at
(Bager 2014; Horton 2003). In addition, anaemia is associated with
the population level, or more directly at vulnerable groups, such
adverse pregnancy and child outcomes (GBDPC 2016). Maternal
as infants, young children, and pregnant women. First, nutrition-
anaemia may lead to greater blood loss during delivery, increased
specific interventions that address the immediate determinants
risk of postpartum haemorrhage, and maternal mortality (Brabin
of anaemia (e.g. poor diet); and second, nutrition-sensitive
2001a). Anaemic mothers are at greater risk of delivering preterm
interventions that address the underlying causes of anaemia
babies and of having a low-birthweight infant (Allen 2000; Haider
(e.g. diseases or infections) (Ruel 2013). This overview of reviews
2013). Anaemia also negatively impacts the cognitive and motor
focused on the former, and included food-based strategies
development of children, and severe anaemia increases the risk of
to control micronutrient malnutrition and increase the intake
child mortality (Brabin 2001b).
of micronutrients through supplementation, food fortification,
Anaemia is a significant public health problem, with prevalence and enhancement of food diversity and quality (WHO/FAO
highest in South Asia and Central and West Africa (Stevens 2013). 2006; Zimmermann 2007). Nutrition-sensitive interventions (i.e.
Estimates from the World Health Organization (WHO) indicate addressing food insecurity, providing access to adequate health
that 800 million children and women were anaemic in 2011 services, ensuring a safe and hygienic environment) were outside
(Stevens 2013; WHO 2015). Although anaemia can occur throughout the scope of this review. Due to the multifactorial causation
the life cycle, young children and pregnant women are the of anaemia, ideally a multisectoral approach, such as the
most vulnerable, with estimated prevalences of 43% and 38%, Strengthening Partnerships, Results, and Innovations in Nutrition
(Review)
Informed decisions.
Globally project (SPRING) supported by USAID would be necessary • Improving dietary diversity and quality
to address anaemia in all its forms (SPRING/USAID 2017). ◦ Increasing food variety through nutrition education and
provision of foods rich in minerals and vitamins such as fruits,
Supplements are taken orally and are intended to supplement vegetables, and iron-rich foods (i.e. red meat, proteins)
the diet with varies micronutrients, alone or in combination, at ◦ Nutrition education and use of iron-pot cooking and fish-
higher doses, to immediately improve nutritional deficiencies and shaped iron ingots
anaemia (Stoltzfus 1998). Fortification refers to the addition of
nutrients to food (e.g. in the form of powders) and beverages, and ◦ General nutrition education and counselling (e.g. increasing
the intake of micronutrient absorption factors and
is another practical way to improve the diet of target populations
decreasing inhibitors of micronutrient absorption)
(WHO/FAO 2006). These interventions show less immediate impact
but are more sustainable and cost-effective over the long term For the purpose of this overview review, we focused on apparently
(Baltussen 2004; WHO/FAO 2006). Iron supplementation and healthy populations with or without anaemia and excluded
fortification have been intensively used and various studies have populations with acute or chronic infections (e.g. malaria, helminth
shown a positive effect on iron status (Man 2021). However, infection, cancer, tuberculosis), inflammation or inherited anaemia
adverse affects such as an increased risk of illness (e.g. diarrhoea (i.e. sickle cell anaemia, thalassaemia).
or inflammation in the gastrointestinal tract), decreased growth
or influence on children's development have been reported How the intervention might work
(Lönnerdal 2017; Paganini 2017).
Supplementation
Cultural norms influence the client’s perspective on their food
Supplements in the form of capsules or drops are provided to
choices and eating patterns. Nutrition education, counselling,
target populations (WHO/FAO 2006). In this way, micronutrients
and promotion aim to increase the intake of foods that are
can be given in the desired quantity and in combination with high
naturally high in certain micronutrients with high bioavailability
bioavailability.
(i.e. the degree to which the micronutrient is absorbed from the
diet and available for the body's functions), and have a high Iron supplementation is used widely, either to prevent ID and
content of factors to improve absorption coupled with a low anaemia in populations at risk (e.g. pregnant women and young
content of inhibiting factors for micronutrient absorption (WHO children), or to improve the haemoglobin status of people
2017). Increasing food diversity is the most desirable and long- with existing anaemia. Four different iron preparations are used
lasting intervention, but efforts to improve dietary quality and frequently for oral supplementation: ferrous sulphate, ferric
to encourage behaviour change may take a long time (WHO/FAO sulphate, ferrous gluconate, and ferrous fumarate. The efficiency of
2006). While improving dietary diversity and quality are important iron supplementation greatly depends on the prevalence of ID and
interventions across the life course, cost and availability of animal anaemia in the area, and interventions have been implemented
products, fruits and vegetables are often the limiting factors for in both low- and middle-income countries. Populations at high
theses interventions. Supplementation or fortification may be the risk of anaemia may especially benefit from iron supplementation;
intervention of choice if more immediate impact on iron status or for example, supplementation during pregnancy can reduce the
anaemia is required. risk of maternal anaemia and ID; however, benefits for infants,
such as a reduced risk of being born premature or with a low
This overview of reviews focuses on the prevention and control of
birthweight, are less clear (Peña-Rosas 2015a). Oral iron therapy
anaemia at all stages of the life cycle, and includes the nutrition-
is often limited due to low adherence and the development of
specific interventions listed below.
side effects, such as nausea and epigastric pain (Beutler 2003).
• Supplementation Alternatively, other iron supplementation regimes, such as lower
◦ Daily or intermittent oral iron, vitamins, or any other mineral dosage or intermittent supplementation, can be used to reduce the
(especially vitamin B12, folate, vitamin A, or provitamin A, but occurrence of side effects (Cavalli-Sforza 2005). In areas with an
also vitamin C, vitamin E, zinc) supplementation alone or in anaemia prevalence of 40% or higher, the WHO recommends the
combination following doses of elemental iron given daily, for three consecutive
months in a year, to prevent ID and anaemia: 10 mg to 12.5 mg for
• Fortification infants and young children aged 6 months to 23 months; 30 mg
◦ Fortification of foods with vitamins and minerals (e.g. iron, for preschool-aged children (24 to 59 months); and 30 mg to 60
folate, vitamin B12, zinc, vitamin A) alone or in combination mg for school-aged children (60 months and older), menstruating
◦ Use of multiple-micronutrient powders (MMNPs; e.g. adult women and adolescent girls (WHO 2016a; WHO 2016b). In
sprinkles or point of use fortification/home fortification settings with a lower anaemia prevalence, the WHO recommends
added to prepared foods at the time of consumption) an intermittent regime (one supplement of elemental iron per week
◦ Provision of supplementary foods containing macronutrients for three consecutive months, followed by three months without
(e.g. protein supplementation) alone or in combination with supplementation, and then three months with supplementation)
micronutrients (e.g. lipid-based nutrient supplementation at the following doses: 25 mg for preschool-aged children (24
(LNS)) to 59 months), 45 mg for school-aged children (60 months and
◦ Provision of fortified complementary foods older), and 60 mg for menstruating women and adolescent girls
(WHO 2017). For pregnant women in areas with a lower anaemia
◦ Provisions of fortified staple foods or beverages (i.e. water)
prevalence (less than 20%), the recommended elemental iron
with micronutrients
supplementation is 120 mg (with folic acid) once a week throughout
◦ Provision of micronutrient, biofortified foods with increased pregnancy to prevent the development of anaemia (WHO 2017).
contents of micronutrients (e.g. iron, zinc, vitamin A) A comprehensive systematic review showed that there was no
(Review)
Informed decisions.
evidence of a difference in the prevalence of anaemia for women to commonly consumed foods (e.g. cereals, salt, milk) (WHO 2017).
receiving intermittent oral iron supplementation during pregnancy In contrast, targeted fortification aims to improve the diet of a
compared with daily supplementation; additionally, intermittent particular subpopulation that is unable to consume high quantities
supplementation was associated with fewer side effects (Peña- of staple foods (i.e. infants and young children), or who have higher
Rosas 2015a). nutritional requirements (i.e. pregnant women, infants, children,
elderly), or both (WHO 2017). Targeted fortification can include
In addition to iron, various other micronutrients are important for the fortification of complementary foods (primarily with iron,
proper function of hematopoesis, and deficiencies may contribute zinc, and calcium) for infants during the transition from exclusive
to the development of anaemia. Primarily, folic acid, vitamin breastfeeding to solid foods (PAHO 2003). Nutrients can be added
A, and vitamin B12 supplements, given alone or in combination to food prior to consumption, in the form of MNPs or sprinkles
with iron supplementation, are used to prevent and control (point-of-use fortification), or consumed in the form of lipid-based
for nutritional deficiencies in conjunction with anaemia. Folic supplements which contain micronutrients, energy, protein, and
acid plays a central role in erythropoiesis, and pregnant women essential fatty acids (WHO 2017). Instead of adding nutrients
especially are at high risk of folic acid deficiency (Fishman 2000). directly to foods, biofortification (through breeding techniques
The WHO recommends daily folic acid supplementation of 400 and genetic modifications) has been used to increase the nutrient
μg with 30 mg to 60 mg elemental iron, or 2800 μg folic acid content (i.e. iron, zinc, provitamin A, amino acids, or protein) of
with 120 mg iron once a week for menstruating women as well crops (e.g. cereals, legumes, tubers) during plant growth (WHO/
as pregnant women to prevent maternal anaemia, puerperal FAO 2006). Iron fortification can include the addition of iron as
sepsis, low birthweight, and preterm birth (WHO 2016c). Vitamin salt or chelates, or the addition of iron-rich components, such as
A acts on several stages of iron metabolism; it increases iron meat, to food products (Prentice 2017). Iron fortification produces
uptake, iron mobilisation, and erythropoiesis (Fishman 2000). some technical difficulties as the addition of the most bioavailable
Supplementation during pregnancy is associated with reduced forms is more expensive, causes unwanted flavour and colour
maternal anaemia for women living in areas with a vitamin A changes, and may react with other food components (Hurrell 2002).
deficiency (McCauley 2015). Likewise, vitamin B12 plays a crucial Hence, less reactive and less expensive iron forms are chosen for
role in erythropoiesis, and severe vitamin B12 deficiency can fortification, but these forms are also less bioavailable (Hurrell
lead to the development of megaloblastic anaemia (Fishman 2002; Zimmermann 2007). Iron doses used for fortification are
2000). Vitamin B12 is only produced by microorganisms, thus lower compared with supplementation and, accordingly, body iron
putting vegetarians, vegans, and populations in settings with levels increase much slower; however, fortification may be overall
low intake of animal products at increased risk of vitamin the safer intervention (Prentice 2017). Most commonly, wheat and
B12 deficiency. There is no consistent recommendation for the maize flour, infant formula, and cereals are fortified with iron (WHO
2016d; WHO/FAO 2006). Other micronutrients, such as folic acid
daily dosage of vitamin B12 supplementation, but commonly
or B vitamins, are also commonly added to wheat flour. Vitamin A
2.4 μg/day is recommended for an adult; a pregnant women has been successfully added to milk or sugar to prevent vitamin A
should add 0.2 μg/day of vitamin B12 to the estimated daily deficiency (Dary 2002; Hombali 2019).
requirement (De Benoist 2008; Van Sande 2013). Other vitamins
and minerals (e.g. vitamin C, vitamin E, zinc, or copper) are Improving dietary diversity and quality
also required for normal enzyme and hematopoietic function,
Dietary diversity refers to the intake of different food or food
and deficiencies in isolation or combination with other vitamins
groups over a defined period of time, and is an essential
and minerals may contribute to the development of nutritional
component of diet quality (FAO 2011; Ruel 2003). Diet quality
anaemia (Fishman 2000). Micronutrients interact in the body to
itself is defined as nutrient adequacy in terms of adequate intake
maintain normal physiological functions and poor diets frequently
of macro- and micronutrients and diet variety at the household
lack several micronutrients at the same time, suggesting that
or individual level (FAO 2011). Insufficient dietary intake or poor
micronutrient deficiencies often occur together. A cost-effective
bioavailability, especially of iron, vitamin A, vitamin B12, and folate,
way of delivering micronutrients, especially for pregnant women,
is through multiple-micronutrient (MMN) supplementation. The are the major causes of nutritional anaemia (WHO 2017). Nutrition
international MMN preparation, UNIMMAP, is used frequently and education and counselling (e.g. meal preparation, increased intake
contains one recommended daily allowance (RDA) of 15 vitamins of micronutrient absorption factors and decreased intake of
and minerals (vitamin A, vitamin B1, vitamin B2, niacin, vitamin inhibitors), combined with the provision of foods rich in minerals
and vitamins such as fruits, vegetables and iron-rich foods (i.e.
B6, vitamin B12, folic acid, vitamin C, vitamin D, vitamin E, copper,
red meat, proteins), aim to stimulate behaviour change and to
selenium, and iodine with 30 mg of iron and 15 mg of zinc) (UNICEF improve dietary diversity and quality (Allen 2008). These food-
1999). While MMN supplementation during pregnancy has been based approaches are potentially simple and sustainable methods
shown to improve birth outcomes, such as low birthweight and for preventing and treating not only IDA but also micronutrient
small-for-gestational weight, there is no clear evidence for a risk malnutrition, though implementation may be challenging due to
reduction of anaemia (Da Silva Lopes 2017; Haider 2017). limited availability, access, and safety of food (WHO 2017). When
educating people in different areas of the world, health educators
Fortification
need to understand micronutrient nutrition and also regional and
Fortification enriches food with nutrients in order to improve local variations in the diet, different cultural practices, different
the nutritional status of populations at risk of micronutrient methods of food processing and meal preparation, and economic
deficiencies (WHO/FAO 2006). Mass fortification approaches constraints (Sharifirad 2011; WHO 2017). Furthermore, these
can reach a large proportion of the population by adding interventions need to take into account the special requirements
micronutrients, such as iron, folic acid, vitamin B12, or vitamin A,
(Review)
Informed decisions.
of subpopulations and vulnerable groups (i.e. young children, Why it is important to do this overview
pregnant women, elderly).
Anaemia is a major public health problem worldwide. Anaemia
Bioavailability of iron refers to total iron in plant or animal food prevalence fluctuates according to various factors, including age,
that is available to the body after digestion and absorption and living area, sex, and socioeconomic status. Through interventions,
depends on the form of iron present in theses foods (Zhang improvement in iron status and anaemia have been made, but
2021). Heme iron is found only in animal-based products and the progress is slow and countries are not on track to meet
has a high bioavailability of approximately 25% to 30%, while the nutrition target for anaemia (Global Nutrition Report 2020).
the bioavailability of non-heme iron in plant and animal products Some types of anaemia are preventable and controllable with
ranges from 1% to 10% (Beck 2014; Heath 2002). Examples of iron- effective interventions. However, a limited number of studies
rich foods include foods of animal (meat and organs, such as liver have looked at the variety of nutrition-specific interventions for
from cattle, fish, fowl, etc.) and non-animal (spinach, legumes, and controlling anaemia and ID throughout the life cycle. Overview
green leafy vegetables) origin. The availability of dietary iron can reviews can provide summaries of research relevant to a decision.
be influenced by various dietary factors, and it is important to Thus, we summarised different nutrition-specific interventions at
promote the consumption of foods that enhance the absorption any stage of life in this Cochrane overview Review. It is important to
and utilisation of iron and reduce the intake of inhibitors. Ascorbic assess the current evidence base to help clarify the best nutrition-
acid (vitamin C) enhances iron absorption through its iron reducing specific intervention for preventing anaemia in order to reduce the
and chelating effects (Teucher 2004). On the other hand, food socioeconomic burden of the condition.
components such as phytate (e.g. in cereals) and calcium can
inhibit iron absorption (Lynch 2000). Tea and coffee, but also red OBJECTIVES
wine and cocoa contain a high amount of polyphenol which have
To summarise the evidence from systematic reviews regarding the
inhibitory effects on iron absorption in the gastrointestinal tract
benefits or harms of nutrition-specific interventions for preventing
(Milman 2020). Consumption of black tea during or after a meal
and controlling anaemia in anaemic or non-anaemic, apparently
reduced iron absorption by 79% to 84% and consumption of coffee
healthy populations throughout the life cycle.
by 39% (Hurrell 1999; Morck 1983). Additionally, milk proteins, egg
proteins, and albumin negatively influence iron absorption (Hurrell METHODS
2010). Therefore, iron in food or supplements is best absorbed in
combination with foods or beverages naturally containing vitamin Criteria for considering reviews for inclusion
C and by avoiding iron inhibitors (Teucher 2004).
We considered all published systematic reviews of randomised
Providing nutrition knowledge is a key step in behaviour change controlled trials (RCTs) of nutrition interventions for preventing and
to establish adequate nutrition and iron intake. Previous studies controlling anaemia.
showed that nutrition education programmes can improve a study
population's knowledge, attitude, and eating behaviour, as well We included both Cochrane Reviews and non-Cochrane Reviews
as haemoglobin levels (Alaofè 2009; Kapur 2003; Nandi 2016; provided they had used a systematic approach, only included RCTs,
Sharifirad 2011; Yusoff 2012). In some regions, fish-shaped iron and assessed the methodological quality of the included trials.
ingots named "Happy Fish" or "Lucky Iron Fish" are commonly We considered systematic reviews with and without meta-analyses
accepted for continuous use in soup or boiling drinking water but excluded meta-analyses without systematic reviews. If the
(Adish 1999; Armstrong 2017). Cooking with iron ingots has been systematic reviews included RCTs and non-RCTs, we included the
shown to release sufficient iron to provide 40% to 75% of the daily systematic reviews which presented results from RCTs separately.
iron requirement for women of reproductive age. The duration We listed eligible systematic reviews in preparation (e.g. published
of boiling iron fish coupled with the water's acidity increases protocols and titles) in Appendix 1 to be included in future updates
iron release; any toxicity with daily use has not been reported of this overview of reviews.
(Armstrong 2017; Charles 2011). However, some studies reported
the production of reactive oxygen species with iron-containing Types of participants
cookware or the risk of iron overload (Alves 2019). Another concern Anaemic or non-anaemic, apparently healthy populations (see
has been the low acceptability of iron pots due to rusting and pot directly below)
weight which could limit the potential of the intervention (Prinsen
2002). • Infants (aged 6 months to 23 months)
• Preschool and school-aged children (aged 2 years to 10 years)
The dietary requirements of vitamin A (retinol) and pro-vitamin A
• Adolescent children (aged 11 to 18 years)
(carotenoids) can be attained by consumption of dark green leafy
vegetables, orange/yellow fruits and vegetables, as well as animal • Adult women
products such as meat, liver, margarine, fish and fish oils, and dairy ◦ Non-pregnant women of reproductive age (aged 19 to 49
products. The fat-soluble vitamin needs to be consumed with lipids years)
to improve its absorption and it is recommended that cooking time ◦ Pregnant women of reproductive age (aged 15 to 49 years)
is reduced to preserve the activity of pro-vitamin A (WHO 2017). ◦ Older adult women (aged 50 to 65 years and above)
• Adult men (aged 19 to 65 years and above)
Meat, fish, poultry, and dairy products are the best sources of
vitamin B12. Folate-rich foods include dark green leafy vegetables, • Mixed population (all ages)
fruits and fruit juices, dairy products, beans, nuts, and grains. We assigned age groups according to the time when the
interventions commenced. Where age groups overlapped but data
(Review)
Informed decisions.
were presented separately, we extracted data according to age Types of comparisons

groups and calculated the mean age of the participants. If this was
We considered all types of comparisons, such as comparison
not the case, we used the mean age of the participants to assign the
of the intervention with placebo, another intervention (e.g.
review into one of the prespecified groups in such a way that most
other minerals and vitamins), co-intervention (provided the co-
participants (e.g. 60%) fell within this group. If this was not possible
intervention is the same in both the intervention and control
or none of the age groups dominated, we assigned this review to
groups), or no intervention (to correct anaemia levels directly or
“mixed population”.
indirectly) or a control group defined by trial authors.
We excluded infants younger than six months of age, since
Types of outcomes
exclusive breastfeeding is recommended from birth until aged
six months. In addition, we excluded populations at risk of We excluded reviews that did not report relevant outcomes from
anaemia due to acute or chronic infections (e.g. malaria, helminth this overview, as preventing and controlling anaemia was a key
infection, cancer, tuberculosis, HIV infection), acquired bone focus for this overview.
marrow disorders, inflammation or inherited anaemia (i.e. blood
disorders such as sickle cell anaemia or thalassaemia), and reviews Primary outcomes
with studies conducted in populations comprising only individuals • Haemoglobin concentration (Hb; in g/L)
with undernutrition (i.e. wasting, stunting, underweight).
• Anaemia (defined per the WHO Hb cut-off for age group (WHO
Types of interventions 2011), and adjusted by altitude, smoking)
• Iron deficiency anaemia (IDA; defined by the presence of
We considered all types of nutrition-specific interventions (i.e.
anaemia plus ID, and diagnosed with an indicator of iron status
interventions that address the immediate determinants of
selected by trial authors)
nutrition) to prevent or correct anaemia, including the following.
Secondary outcomes
• Supplementation
◦ Daily or intermittent oral iron, vitamins, or any other mineral • Iron deficiency (ID; defined by trial authors and measured using
(especially vitamin B12, folate, vitamin A, or provitamin A, but indicators of iron status, such as ferritin or transferrin)
also vitamin C, vitamin E, zinc) supplementation alone or in • Severe anaemia (defined per the WHO Hb cut-off for age group
combination (WHO 2011))
• Fortification • Adverse effect (any adverse effects, including side effects, all
◦ Fortification of foods with vitamins and minerals (e.g. iron, gastrointestinal symptoms, diarrhoea, vomiting, constipation,
folate, vitamin B12, zinc, vitamin A) alone or in combination as defined by trial authors)
◦ Use of multiple-micronutrient powders (MMNPs; e.g.
Search methods for identification of reviews
sprinkles or point-of-use fortification/home fortification
added to prepared foods at the time of consumption) We first searched the following sources in July 2018. We ran top-up
◦ Provision of supplementary foods containing macronutrients searches of each source in August 2020 and September 2020 apart
(e.g. protein supplementation) alone or in combination with from DARE and POPLINE, which have both ceased publication.
micronutrients (e.g. lipid-based nutrient supplementation
(LNS)) • Cochrane Database of Systematic Reviews (CDSR; 2020 Issue 8)
part of the Cochrane Library (searched 25 August 2020)
◦ Provision of fortified complementary foods
• MEDLINE via Ovid (1946 to August 2020 week 2)
◦ Provision of fortified staple foods or beverages (i.e. water)
with micronutrients • MEDLINE In-Progress and other Non-Indexed Citations via Ovid
(searched 25 August 2020)
◦ Provision of micronutrient, biofortified foods with increased
contents of micronutrients (e.g. iron, zinc, vitamin A, protein) • MEDLINE Epub Ahead of Print via Ovid (current issue; searched
25 August 2020)
• Improving dietary diversity and quality
◦ Increasing food variety through nutrition education and • Embase via Ovid (1974 to 25 August 2020)
provision of foods rich in minerals and vitamins, such as • CINAHL via EBSCOhost (Cumulative Index to Nursing and Allied
fruits, vegetables, and iron-rich foods (i.e. red meat, proteins) Health Literature; (1937 to 25 August 2020))
◦ Nutrition education and use of iron-pot cooking and fish- • Database of Abstract of Reviews of Effects (DARE; 2015, Issue 4.
shaped iron ingots Final Issue) part of the Cochrane Library (searched 24 July 2018)
◦ General nutrition education and counselling (e.g. increasing • Campbell Collaboration Online Library
the intake of micronutrient absorption factors and (www.campbellcollaboration.org/better-evidence.html;
decreasing inhibitors of micronutrient absorption) searched 15 September 2020)
• 3ie International Initiative for Impact Evaluation
Nutrition-sensitive interventions, i.e. interventions that address (www.3ieimpact.org; searched 15 September 2020)
the underlying determinants of nutrition, such as food insecurity,
• Epistemonikos (www.epistemonikos.org; searched 25 August
inadequate healthcare services or an unsafe and unhygienic
2020)
environment, were outside the scope of this review.
• POPLINE (www.popline.org; searched 24 July 2018)
• PROSPERO (www.crd.york.ac.uk/prospero; searched 25 August
2020)
(Review)
Informed decisions.
The search strategies are listed in Appendix 2. We presented the review details and results in tables according
to age group and type of intervention. Another review author
We searched for other relevant reviews in the reference lists of the (EO) verified the extracted data. We resolved any discrepancies
included reviews, as well as the references of relevant narrative through discussion until we reached a consensus, or, if necessary,
reviews and guidelines. We did not apply any restrictions on by consulting another review author (EO).
language or publication date.
Where any information from the reviews was unclear or missing, we
Data collection and analysis accessed the published papers of the individual trials.
The methods we used for data collection and analysis, as described Assessment of methodological quality of included reviews
in successive sections, are based on the Cochrane Handbook for
Systematic Reviews of Interventions (Higgins 2021). We assessed both the quality of evidence in the included reviews
(by assessing the risk of bias of the included trials in each review
In successive sections, we report only the methods that we used in and the GRADE certainty ratings of the evidence, if provided),
this review. Please see our protocol, Da Silva Lopes 2018, and Table and the methodological quality of the systematic reviews (using
1 for additionally planned but unused methods. AMSTAR: A MeaSurement Tool to Assess systematic Reviews; Shea
2007a; Shea 2007b; Shea 2009).
Selection of reviews
Quality of the evidence in included reviews
In order to identify all relevant published systematic reviews of
RCTs assessing the effects of nutrition-specific interventions to Five review authors (KL, YT, NY, MS, and OR) independently
prevent and control anaemia throughout the life cycle, six review assessed the quality of the evidence in the included reviews.
authors (KL, YT, NY, MS, OR, and WM) independently screened titles We summarised the methods used to assess random sequence
and abstracts, and assessed the full texts of all identified systematic generation, allocation concealment, blinding of participants and
reviews for eligibility. We assessed the reviews' objectives and personnel, blinding of outcome assessment, incomplete outcome
methods, including outcomes and participants, for relevance and data, selective reporting, and other potential sources of bias. If
included only those reviews that met the criteria listed above provided in the included systematic reviews, we also extracted
(under Criteria for considering reviews for inclusion). GRADE ratings for our primary and secondary outcomes, to assess
the certainty of the evidence.
Where systematic reviews were similar in relation to research
question, participants and interventions, we chose the most Quality of included reviews
comprehensive review, provided there was an overlap between the
underlying studies included in the individual reviews. Five review authors (KL, YT, NY, MS, and OR) independently assessed
the methodological quality of the included reviews using AMSTAR
We resolved any disagreements through discussion until we (Shea 2007a; Shea 2007b; Shea 2009). AMSTAR assesses the degree
reached a consensus, or, if necessary, we consulted another review to which review methods avoided bias by evaluating the methods
author (EO). against 11 distinct criteria (shown below).
The selection process is reported in the PRISMA flow diagram • Was an a priori design provided?
(Moher 2009). • Was there duplicate study selection and data extraction?
• Was a comprehensive literature search performed?
Data extraction and management
• Was the status of publication (i.e. grey literature) used as an
We generated a data extraction form and pilot tested it. After inclusion criterion?
verification, five review authors (KL, YT, NY, MS, and OR) • Was a list of studies (included and excluded) provided?
independently extracted data from the included reviews on the
• Were the characteristics of the included studies provided?
following.
• Was the scientific quality of the included studies assessed and
• Characteristics of included systematic reviews: date of search; documented?
numbers of participants and included trials; review objective(s); • Was the scientific quality of the included studies used
type of participants; setting (countries, anaemia and malaria appropriately in formulating conclusions?
prevalence); interventions; comparisons; relevant outcomes • Were the methods used to combine the findings of studies
with definition and information for any adjustments; GRADE appropriate?
assessment of relevant outcomes • Was the likelihood of publication bias assessed?
• Risk of bias assessment in included systematic reviews: method • Was the conflict of interest stated?
used; domains assessed; judgements
• Characteristics of interventions: population (mean age, Each item on AMSTAR is rated as yes (clearly done), no (clearly not
anaemia status/prevalence, known micronutrient deficiencies); done), cannot answer, or not applicable (Shea 2007a; Shea 2007b;
prevention or treatment; dosage or form of application Shea 2009). We used this assessment to interpret the results of the
(including compound, formulation); frequency; start and reviews. We resolved any discrepancies through discussion until we
duration of intervention; adherence to intervention reached a consensus, or, if necessary, by consulting another review
• Results of included reviews: comparison; outcome; numbers of author (EO).
trials and participants; results (from meta-analysis or narrative
description)
(Review)
Informed decisions.
Data synthesis RESULTS

We provided a narrative summary of the data from the individual
Description of included reviews
reviews for our primary and secondary outcomes and presented
these summaries using tables. We presented data according to For this overview of reviews, we searched for Cochrane and
age group. Within each age category, we summarised the results non-Cochrane systematic reviews of RCTs of nutrition-specific
from the different systematic reviews according to the types of interventions to control or prevent anaemia at any stage of life.
interventions (supplementation, fortification, improving dietary In total, we identified 9588 records from database searching. After
diversity and quality). We described the results separately for removal of 2719 duplicates, we screened 6869 titles and abstracts.
interventions versus placebo or no intervention, and interventions We excluded 6607 records at this stage and screened 262 full
versus another intervention. We investigated heterogeneity in texts against our inclusion and exclusion criteria (see Criteria
relation to setting and population characteristics (e.g. prevalence for considering reviews for inclusion). We excluded 107 clearly
of anaemia, malaria or other infectious diseases, baseline irrelevant records plus an additional 62 records that we decided
anaemia status, micronutrient deficiencies), features of the did not meet the inclusion criteria following closer inspection; we
intervention (e.g. type, compound, dose, frequency, duration), and summarise these 62 studies, with reasons for their exclusion, in
comparator (e.g. placebo, co-interventions, other interventions, Table 2. Eighteen ongoing reviews have been listed in Appendix
no intervention). If the authors of the individual reviews had 1. Finally, we included 75 systematic reviews in the review. The
not adjusted the data on anaemia for altitude and smoking, we selection process is shown in Figure 1.
presented the data in the form provided and noted this in the
'Results' and 'Discussion' sections of the review.
(Review)
Informed decisions.
Figure 1. Study flow diagram.
(Review)
Informed decisions.
Objectives and scope of included reviews deficiencies. In Aaron 2015, children's anaemia status and known
micronutrient deficiencies at baseline were not reported.
We summarised the key characteristics of the included reviews in
Table 3, Table 4, Table 5, Table 6, Table 7 and Table 8. Reviews aimed Adolescent children (aged 11 to 18 years)
to assess nutrition-specific interventions to prevent or control
anaemia at different stages of life. All reviews included one or Four reviews included adolescent children aged 11 to 18 years
more of our primary outcomes: haemoglobin (Hb) concentration, (Fernández-Gaxiola 2019; Neuberger 2016; Salam 2016; Salam
anaemia and iron deficiency anaemia (IDA), and our secondary 2020). Fernández-Gaxiola 2019 included anaemic and non-anaemic
outcomes: iron deficiency (ID), severe anaemia and adverse effects. menstruating women and some included trials reported on ID at
Although two reviews met our inclusion criteria, they did not baseline. Neuberger 2016 included a mixed population of anaemic
contribute any data (Abe 2016; De-Regil 2015). and non-anaemic children. In Salam 2016, two trials included
anaemic girls while the remaining 29 trials did not report the
Among the 75 included systematic reviews: children's anaemia status and known micronutrient deficiencies
at baseline. Salam 2020 did not describe the children's anaemia
• 54 reviews reported Hb concentration; status.
• 45 reviews reported anaemia;
Non-pregnant women of reproductive age (aged 19 to 49 years)
• 18 reviews reported IDA;
• 4 reviews reported severe anaemia; Five reviews included non-pregnant women between 19 and 49
years of age (Abe 2016; Houston 2018; Lassi 2020; Low 2016; Sultan
• 23 reviews reported ID; and
2019). In Abe 2016, the population consisted of non-pregnant
• 23 reviews reported adverse effects. mothers of unknown anaemia or micronutrient deficiency status
Study characteristics at baseline who either exclusively breastfed or practised mixed
feeding. Houston 2018 included iron-deficient but non-anaemic
The included reviews were conducted between 2003 (Geerligs adult women. Lassi 2020 included women of reproductive age with
2003) and 2020 (Arabi 2020; Field 2020; Lassi 2020; Salam 2020; unknown anaemia or micronutrient deficiency status at baseline.
Suchdev 2020). The number of trials in the included reviews ranged Low 2016 included a mixed population of anaemic and non-
from two (Abdullah 2013; Abe 2016; Suchdev 2015) to 90 (Petry anaemic and iron-deficient menstruating women between 13 and
2016b). Of the 55 reviews, 54 included randomised controlled 45 years, but only three of the 67 trials included adolescent girls.
trials (RCTs) and Suchdev 2015 included only cluster-RCTs. Thirty- Sultan 2019 targeted women with a postdelivery and Hb level less
two included RCTs and cluster-RCTs, 18 reviews quasi-RCTs, and than 12g/dL.
two reviews included cross-over RCTs (Mayo-Wilson 2014a; Tolkien
2015). Das 2019a included RCTs and quasi-RCTs. Five reviews Pregnant women of reproductive age (aged 15 to 49 years)
(Das 2019b; Field 2020; Peña-Rosas 2019; Sadighi 2019; Tablante Twenty-three reviews included pregnant women (Abu Hashim
2019) included randomised and non-randomised trials, including 2017; Bhutta 2012; Buppasiri 2015; Daru 2016; Das 2018; De-Regil
observational studies (see Table 3, Table 4, Table 5, Table 6, Table 2015; Govindappagari 2019; Haider 2011; Haider 2013; Imdad 2012;
7 and Table 8). Keats 2019; Lassi 2013; McCauley 2015; Peña-Rosas 2015a; Peña-
Rosas 2015b; Qassim 2018; Qassim 2019; Radhika 2019; Reveiz
Populations
2011; Rumbold 2015; Shi 2015; Suchdev 2015; Thorne-Lyman
The number of participants in the included reviews ranged from 52 2012). The majority of reviews included pregnant women of any
in Abe 2016 to over 310,000 in McCauley 2015. gestational age; only two reviews did not report the gestational
age of women (Imdad 2012; Shi 2015). Ten reviews included a
Infants (aged 6 to 23 months) mixed population of anaemic and non-anaemic pregnant women
Thirteen reviews included infants aged 6 to 23 months at the start of (Abu Hashim 2017; Daru 2016; Das 2018; Keats 2019; McCauley
the interventions (Abdullah 2013; Das 2019a; Dekker 2010; Dewey 2015; Peña-Rosas 2015a; Peña-Rosas 2015b; Reveiz 2011; Shi 2015;
2009; Eichler 2012; Kristjansson 2015; Matsuyama 2017; Pasricha Thorne-Lyman 2012). Four reviews included a small number of
2013; Petry 2016b; Pratt 2015; Salam 2013; Shapiro 2019; Suchdev women with known ID (Daru 2016; Haider 2013; Keats 2019;
2020). Abdullah 2013, De-Regil 2017 and Petry 2016b included Reveiz 2011). Some women with vitamin A deficiency were
apparently healthy infants. Dekker 2010, Dewey 2009, Eichler 2012, included in two reviews (Keats 2019; McCauley 2015) and vitamin
Kristjansson 2015, Matsuyama 2017 and Pasricha 2013 assessed C deficiency in one review (Rumbold 2015). Anaemic status at
mixed populations of anaemic and non-anaemic infants with or baseline was not reported in 10 reviews (Bhutta 2012; Buppasiri
without known micronutrient deficiencies. Das 2019a included 2015; Das 2018; De-Regil 2015; Haider 2011; Haider 2013; Imdad
non-hospitalised infants and young children aged 6 months to 23 2012; Lassi 2013; Rumbold 2015; Suchdev 2015), and known
months. In Pratt 2015 and Salam 2013, infant's anaemia status and micronutrient deficiencies were not reported in 17 reviews (Abu
known micronutrient deficiencies at baseline were not reported. Hashim 2017; Bhutta 2012; Buppasiri 2015; Das 2018; De-Regil
2015; Govindappagari 2019; Haider 2011; Haider 2013; Lassi 2013;
Preschool and school-aged children (aged 2 to 10 years) Peña-Rosas 2015a; Peña-Rosas 2015b; Qassim 2018; Qassim 2019;
Radhika 2019; Shi 2015; Suchdev 2015; Thorne-Lyman 2012).
Eight reviews included children aged 2 to 10 years of age at the start
of the interventions (Aaron 2015; Das 2013a; De-Regil 2011; De-Regil Older adult women (aged 50 to 65 years and above)
2017; Eichler 2019; Low 2013; Mayo-Wilson 2014a; Thompson 2013).
Das 2013a, De-Regil 2011, De-Regil 2017, Low 2013, Mayo-Wilson None of the included reviews included older adult women only.
2014a and Thompson 2013 included a mixed population of anaemic
and non-anaemic children with or without known micronutrient
(Review)
Informed decisions.
Adult men (aged 19 to 65 years and above) did not report on anaemia and malaria prevalence in the included
None of the included reviews included adult men only. trials.
Adolescent children (aged 11 to 18 years)

Twenty-two reviews included a mixed population where it was Fernández-Gaxiola 2019 and Salam 2016 included trials conducted
not possible to include the reviews in any of the specific age in low-, middle-, and high-income countries. Neuberger 2016 and
groups above (Arabi 2020; Basutkar 2019; Casgrain 2012; Das Salam 2020 included trials conducted in low- and middle-income
2019b; Field 2020; Finkelstein 2019; Garcia-Casal 2018; Geerligs countries. In Fernández-Gaxiola 2019, five of the 25 included
2003; Gera 2007a; Gera 2009; Gera 2012; Hess 2016; Huo 2015; trials were conducted in malaria-endemic areas and one RCT
Peña-Rosas 2019; Ramírez-Luzuriaga 2018; Sadighi 2019; Silva Neto reported anaemia prevalence. Neuberger 2016 included a mixed
2019; Smelt 2018; Tablante 2019; Tay 2015; Tolkien 2015; Yadav adolescents, with or without anaemia, and with or without malaria
2019). Field 2020 included a general population aged two years or parasitaemia. Salam 2016 and Salam 2020 did not report
and above. Gera 2007a and Gera 2009 included children of any anaemia and malaria prevalence in the included trials.
age between birth and 19 years. Garcia-Casal 2018, Silva Neto Non-pregnant women of reproductive age (aged 19 to 49 years)
2019 and Hess 2016 included children and adults. Casgrain 2012
and Tolkien 2015 included adults, while Smelt 2018 and Tay 2015 Four reviews included trials conducted in low-, middle, and high-
focused on older adults. Basutkar 2019 included patients with income countries, and none of the reviews reported anaemia and
IDA aged 20 to 45 years. The remaining 11 reviews included any malaria prevalence in the included trials (Abe 2016; Houston 2018;
population (Arabi 2020; Das 2019b; Finkelstein 2019; Geerligs 2003; Low 2016; Sultan 2019). Lassi 2020 included trials conducted in low-
Gera 2012; Huo 2015; Peña-Rosas 2019; Ramírez-Luzuriaga 2018; and middle-income countries, and none described anaemia and
Sadighi 2019; Tablante 2019; Yadav 2019). All reviews reported to malaria prevalence.
have included a mixed population of anaemic and non-anaemic
Pregnant women of reproductive age (aged 15 to 49 years)
participants, except Ramírez-Luzuriaga 2018 where anaemia status
at baseline was not reported. ID at baseline was described in Nine reviews included trials conducted in low- and middle-income
seven reviews (Basutkar 2019; Casgrain 2012; Geerligs 2003; Gera countries (Abu Hashim 2017; Bhutta 2012; Das 2018; Haider 2011;
2007a; Gera 2012; Huo 2015; Silva Neto 2019). Some participants McCauley 2015; Radhika 2019; Shi 2015; Suchdev 2015; Thorne-
were vitamin B12 deficient and folate deficient in Smelt 2018. Lyman 2012), and 12 in low-, middle-, and high-income countries
In Gera 2009, known micronutrient deficiency was reported, but (Buppasiri 2015; De-Regil 2015; Govindappagari 2019; Haider 2013;
not further described. In Garcia-Casal 2018, all included trials Imdad 2012; Keats 2019; Lassi 2013; Peña-Rosas 2015a; Peña-
were conducted in areas with high prevalence of micronutrient Rosas 2015b; Qassim 2018; Qassim 2019; Rumbold 2015); two
deficiencies, especially iron. The remaining four reviews did not reviews did not report the setting of the included trials (Daru 2016;
report on known micronutrient deficiencies (Hess 2016; Ramírez- Reveiz 2011). Trials included in Haider 2013 were conducted in
Luzuriaga 2018; Tay 2015; Tolkien 2015). anaemia and malaria prevalent settings. McCauley 2015, Peña-
Rosas 2015a, Peña-Rosas 2015b, and Thorne-Lyman 2012 included
Setting trials conducted in malaria-endemic areas, but did not report on
Infants (aged 6 to 23 months)
anaemia prevalence. Suchdev 2015 reported that malaria was not
endemic in the areas where the trials were conducted. Seventeen
Of the 13 included reviews for this age group, seven included reviews did not report on anaemia and malaria prevalence in the
trials conducted in low- and middle-income countries (Abdullah included trials (Abu Hashim 2017; Bhutta 2012; Buppasiri 2015; Das
2013; Suchdev 2020; Das 2019a; Dekker 2010; Kristjansson 2015; 2018; Daru 2016; De-Regil 2015; Govindappagari 2019; Haider 2011;
Salam 2013; Shapiro 2019) and five in low-, middle-, and high- Imdad 2012; Keats 2019; Lassi 2013; Qassim 2018; Qassim 2019;
income countries (Dewey 2009; Eichler 2012; Matsuyama 2017; Radhika 2019; Reveiz 2011; Rumbold 2015; Shi 2015).
Pasricha 2013; Pratt 2015); one review did not report the setting
of the included trials (Petry 2016b). In Suchdev 2020, Dekker 2010, Mixed population (all ages)
Dewey 2009 and Pasricha 2013, the included trials were conducted Six reviews included trials conducted in low- and middle-income
in anaemia and malaria prevalent settings. Anaemia and malaria countries (Garcia-Casal 2018; Geerligs 2003; Hess 2016; Huo 2015;
prevalence was not described in nine reviews (Abdullah 2013; Das Ramírez-Luzuriaga 2018; Yadav 2019), 11 in low-, middle-, and high-
2019a; Eichler 2012; Kristjansson 2015; Matsuyama 2017; Petry income countries (Arabi 2020; Basutkar 2019; Casgrain 2012; Das
2016b; Pratt 2015; Salam 2013; Shapiro 2019). 2019b; Field 2020; Finkelstein 2019; Gera 2007a; Gera 2009; Gera
Preschool and school-aged children (aged 2 to 10 years)
2012; Sadighi 2019; Silva Neto 2019), and one review, Smelt 2018,
included trials conducted in high-income countries. Four reviews
Four reviews included trials that were conducted in low- and did not report the setting of the included trials (Peña-Rosas 2019;
middle-income countries (Aaron 2015; De-Regil 2011; De-Regil Tablante 2019; Tay 2015; Tolkien 2015). Geerligs 2003 included one
2017; Thompson 2013) and four included trials from low-, middle-, trial conducted in a malaria-endemic area, but did not report on
and high-income countries (Das 2013a; Eichler 2019; Low 2013; anaemia prevalence in the included trials. In Garcia-Casal 2018,
Mayo-Wilson 2014a). De-Regil 2011, Low 2013 and Thompson 2013 two trials reported 40% or higher prevalence on anaemia and three
included trials that were conducted in malaria-endemic areas, but less than 20%, and two trials were conducted in malaria-endemic
did not report on anaemia prevalence. De-Regil 2017 and Mayo- areas. Trials included in five reviews were conducted in settings
Wilson 2014a included trials conducted in anaemia and malaria where anaemia is prevalent, but the reviews did not report on
prevalence settings, while Aaron 2015, Das 2013a and Eichler 2019 malaria prevalence (Gera 2007a; Gera 2009; Gera 2012; Hess 2016;
Huo 2015). In Field 2020, two trials conducted in non-malaria-
(Review)
Informed decisions.
endemic areas, while other trials did not report on malaria. In Preschool and school-aged children (aged 2 to 10 years)
Peña-Rosas 2019, one trial conducted in malaria-endemic areas Four reviews assessed supplementation interventions (De-Regil
but malaria prevalence was not reported. Nine reviews did not 2011; Low 2013; Mayo-Wilson 2014a; Thompson 2013). Three
report on anaemia and malaria prevalence in the included trials reviews assessed oral iron supplementation (De-Regil 2011; Low
(Arabi 2020; Casgrain 2012; Das 2019b; Finkelstein 2019; Ramírez- 2013; Thompson 2013). De-Regil 2011 included trials that used
Luzuriaga 2018; Silva Neto 2019; Smelt 2018; Tablante 2019; Yadav 7.5 mg to 200 mg elemental iron (ferrous sulphate in most trials)
2019). Tay 2015 and Tolkien 2015 did not report on anaemia or weekly, or two to three times per week, for a period of 6 weeks to
malaria prevalence, but the trials included anaemic participants. 12 months. Low 2013 investigated the effects of daily 5 mg to 400
Interventions mg of elemental iron (ferrous sulphate in most trials) for one to
12 months. Thompson 2013 also assessed 5 mg to 50 mg of daily
We summarise the key characteristics of the interventions included ferrous sulphate (in most trials) given at least five times per week
in the reviews in Table 9; Table 10; Table 11; Table 12; Table 13 and for a period of 28 days to 15 months.
Table 14.
Four reviews assessed fortification interventions (Aaron 2015;
Infants (aged 6 to 23 months) Das 2013a; De-Regil 2017; Eichler 2019). In Aaron 2015, trials
Five reviews assessed supplementation interventions (Abdullah investigated the effects of daily, non-dairy, multiple-micronutrient
2013; Das 2019a; Dekker 2010; Pasricha 2013; Petry 2016b). In (MMN)-fortified beverages for a duration of 8 weeks to 8.5 months.
Abdullah 2013, the intervention included iron supplementation Das 2013a assessed food fortification with zinc, including 3.75 mg/
with 3 mg/kg/day ferrous sulphate for three to four months. Das oz of zinc oxide in cereals, 400 mg/loaf of zinc acetate in bread and 5
2019a assessed the effects of daily small quantity lipid-based mg zinc in 100 mg porridge, for a duration of three to nine months.
nutrient supplementation (LNS) (110 to 120 kcal/day; 20 g dose) De-Regil 2017 included trials assessing daily MNP for point-of-use
and medium quantity LNS (250 to 500 kcal/day; 45 g to 90 g dose) fortification for 8 to 12 weeks. Eichler 2019 evaluated the effects
for 7 to 18 months. Pasricha 2013 also investigated the effects of the centrally-processed fortified dairy products and fortified
of supplementation with daily iron, with iron doses ranging from cereals, using any fortification strategy.
12.5 mg to > 60 mg (ferrous sulphate in most trials), for 1 week Adolescent children (aged 11 to 18 years)
to 14 months. Petry 2016b assessed daily iron supplements of
not more than 15 mg iron/day. One review assessed daily zinc Four reviews examined supplementation interventions
supplementation (typically 10 mg to 20 mg of zinc), with the (Fernández-Gaxiola 2019; Neuberger 2016; Salam 2016; Salam
duration of the intervention ranging from 4 to 15 months (Pasricha 2020). Fernández-Gaxiola 2019 included trials assessing the effects
2013). of oral iron alone or with other vitamins and minerals, using mostly
10 mg to 120 mg of ferrous sulphate; the intervention period
Five reviews assessed fortification interventions (Dewey 2009; ranged between 3 months or less and up to 12 months. Neuberger
Eichler 2012; Matsuyama 2017; Salam 2013; Suchdev 2020). 2016 evaluated the effects of oral iron supplementation with or
Suchdev 2020 included trials assessing the effect of daily without folic acid and oral iron supplementation with antimalarial
micronutrient powders (MNPs) with 12.5 mg elemental iron for 2 to prophylaxis. Salam 2016 investigated daily or weekly micronutrient
12 months. Salam 2013 also investigated daily MNP interventions supplementation, where most trials used iron or iron and folic
with 12.5 mg iron as ferrous fumarate (range 2.5 mg to 30 mg) acid alone or in combination with other micronutrients. That
for 2 to 24 months. In Dewey 2009, trials included daily home review also assessed the effect of micronutrient supplementation
fortification of complementary foods with at least 12.5 mg iron in for adolescent pregnant women commencing between 20 and
MNP (sprinkles), crushable tablets, and lipid-based or soy-based 27 weeks' gestation until delivery. Salam 2020 also investigated
products for 6 weeks up to 20 months. Matsuyama 2017 included daily or weekly micronutrient supplementation alone, such as iron,
trials assessing the effect of fortified milk (most common with iron, calcium, folic acid, zinc, vitamin A, and vitamin D or in combination
vitamin C, zinc, fatty acids, vitamin D, probiotics or synbiotics) given with other micronutrients.
for 4 to 12 months without specifying the iron dose and frequency
of the interventions. Another review examined daily micronutrient- Non-pregnant women of reproductive age (aged 19 to 49 years)
fortified milk or cereal food with 1.8 mg/day to 27.5 mg/day iron, Five reviews assessed supplementation interventions (Abe 2016;
with a mean follow-up period of 8.25 months (Eichler 2012). Houston 2018; Lassi 2020; Low 2016; Sultan 2019). In Abe 2016,
included trials assessed the effect of daily, MMN supplementation
One review included supplementation and fortification
with 18 mg to 45 mg iron for 6 to 15 weeks postpartum. Houston
interventions and included daily micronutrient sprinkles with
2018 assessed daily iron therapy for 46 days, including oral
12.5 mg iron, iron-fortified milk with 5.28 mg to 5.8 mg ferrous
supplementation with 16 mg/day to 200 mg/day iron, intravenous
gluconate, daily or weekly iron supplementation with 10 mg to 12.5
(IV) with 200 mg/day to 1000 mg/day iron, and intramuscular (IM)
mg iron and food-based strategies for an average duration of six
with 100 mg/day iron. Lassi 2020 evaluated the effects of daily
months (Pratt 2015).
and weekly iron folic acid supplementation. This review included
Two reviews focused on improving dietary diversity and quality a variety of studies which used different dosages of iron and
(Kristjansson 2015; Shapiro 2019). Kristjansson 2015 assessed them folic acid supplementation. Low 2016 investigated daily oral iron
through daily supplementary feeding (provision of energy and supplementation alone or with folic acid or vitamin C, with 1
macronutrients), with or without added micronutrient, for 3 to mg to 300 mg of elemental iron, where half of the trials used
32 months. Shapiro 2019 evaluated the effects of consumption of ferrous sulphate and the remaining trials a variety of different iron
animal-source foods compared with no animal-source foods, such formulations. The interventions lasted between 1 and 24 weeks.
as a plant-source foods or no intervention.
(Review)
Informed decisions.
Sultan 2019 investigated the effects of the iron IV formulation delivery and up to 24 weeks after delivery. McCauley 2015
compared with oral iron supplementation. and Thorne-Lyman 2012 investigated vitamin A supplementation
during pregnancy. In McCauley 2015, trials assessed daily or weekly
Pregnant women of reproductive age (aged 15 to 49 years) vitamin A, alone or in combination with other supplements, mainly
Twenty-two reviews assessed supplementation interventions in as capsules of 5750 IU to 444,000 IU of vitamin A, starting from trial
pregnant women (Abu Hashim 2017; Bhutta 2012; Buppasiri 2015; enrolment for a duration of 8 to 12 weeks up to 6 weeks postpartum.
Daru 2016; Das 2018; De-Regil 2015; Govindappagari 2019; Haider Thorne-Lyman 2012 investigated daily or weekly supplementation
2011; Haider 2013; Imdad 2012; Keats 2019; Lassi 2013; McCauley with vitamin A (3333 IU/day to 10,000 IU/day) or carotenoids (or
2015; Peña-Rosas 2015a; Peña-Rosas 2015b; Qassim 2018; Qassim both) starting between 12 to 39 weeks' gestation. In De-Regil
2019; Radhika 2019; Reveiz 2011; Rumbold 2015; Shi 2015; Thorne- 2015, the included trials assessed daily periconceptional folate or
Lyman 2012). Any form of iron supplementation or treatment was folic acid supplementation alone or in combination with other
assessed in 11 reviews (Daru 2016; Govindappagari 2019; Haider vitamins or minerals, using 0.4 mg to 4.0 mg folic acid, starting at
2013; Imdad 2012; Peña-Rosas 2015a; Peña-Rosas 2015b; Qassim preconception until 12 weeks' gestation. Lassi 2013 also focused
2018; Qassim 2019; Radhika 2019; Reveiz 2011; Shi 2015). Daru 2016 on daily folic acid supplementation with 10 μg to 400 μg folic acid,
studied iron treatment (oral, including fortified water, IV or IM) for with or without iron or other vitamins and minerals, starting from
pregnant women with ID anaemia using weekly 200 mg to 400 eight weeks' gestation or from at least 20 weeks' gestation and
mg IV iron or 120 mg oral iron and 30 mg to 80 mg of oral iron continuing throughout pregnancy. One review focused on calcium
for women with non-anaemic ID on a weekly or daily basis until supplementation, with daily doses ranging from 300 mg to 2000 mg,
28 weeks' gestation. Govindappagari 2019 included trials using IV using calcium carbonate, calcium gluconate or calcium lactate; the
iron (iron sucrose, ferric carboxymaltose, low molecular weight iron interventions started at around 20 weeks' gestation and lasted until
dextran) infused in split doses every other day, with a maximum delivery (Buppasiri 2015). Rumbold 2015 investigated daily vitamin
daily dose of 200 mg. In Haider 2013, included trials assessed the C supplementation alone or in combination with other vitamins
effect of daily iron supplementation (10 mg to 240 mg) with or and minerals; the included trials commonly used 1000 mg/day (250
without folic acid, starting before 21 weeks' gestation up to 30 mg to 2000 mg) starting in the second trimester. Another review
weeks' gestation. Imdad 2012 also looked at trials assessing iron assessed the effect of bovine lactoferrin, 100 mg twice a day or
supplementation with or without folic acid using 20 mg/day to 250 mg once a day, starting in the second or third trimester with
300 mg/day from no later than 28 weeks' gestation; however, the intervention lengths of four to eight weeks (Abu Hashim 2017).
length of the interventions was not reported. Peña-Rosas 2015b Only one review focused on fortification and assessed daily MNP
included trials using daily iron supplements, with doses ranging for point-of-use fortification of semi-solid foods starting at 14 to
from 9 mg to 900 mg, and that commenced before 20 weeks' 24 weeks' gestation until 32 weeks' gestation or three months
gestation until delivery or postpartum. Peña-Rosas 2015a assessed postpartum (Suchdev 2015).
intermittent iron supplementation, and iron doses in the included
trials ranged from 80 to 300 mg elemental iron given once a week,
starting before 20 weeks' gestation, and lasting for at least 10 weeks Nine reviews assessed supplementation interventions (Arabi 2020;
or until delivery. Qassim 2018 and Qassim 2019 included trials Basutkar 2019; Casgrain 2012; Gera 2007a; Gera 2009; Silva Neto
involving administration of daily IV iron (ferric carboxymaltose, 2019; Smelt 2018; Tay 2015; Tolkien 2015). Casgrain 2012 included
iron polymaltose or iron sucrose). Radhika 2019 also focused on trials assessing 3-week to 24-week long iron interventions in
daily IV iron sucrose. Reveiz 2011 included trials assessing any iron healthy adults, including daily or weekly iron supplementation
intervention (oral, oral iron plus adjuncts, IM, IV, blood transfusion, using 5 mg to 240 mg iron, mainly as ferrous sulphate, iron
recombinant erythropoietin) using different iron doses: daily or fortification of rice, wheat-based snacks or fish sauce with 1.42
weekly oral iron 20 mg to 300 mg; IM iron dose depending on body mg to 27.9 mg iron, or rich natural dietary sources such as meat.
weight and Hb deficit and injected on alternating day; IV maximum Gera 2007a investigated iron interventions for children from birth
total dose of iron ranged from 200 mg to 500 mg injected every other to 19 years old, including oral iron supplementation, parenteral
day or twice weekly. The interventions started between 16 and 34 route or as formula, milk, or cereals fortified with 5 mg/day to
weeks' gestation and lasted for 4 to 16 weeks or up to delivery. 120 mg/day iron for a period of 1 week to 12 months. Gera 2009
Shi 2015 looked at trials comparing IV iron sucrose treatment focused on iron supplementation for children from birth to 18 years
every other day with 100 mg to 300 mg daily elemental iron as old, with 5 mg/day to 60 mg/day iron in combination with two
ferrous sulphate, iron polymaltose complex or ferrous fumarate for or more MNs, for a duration of 3 weeks to 12 months. Another
a duration of four to six weeks without specifying the starting time. review assessed daily iron supplementation compared with dietary
intervention (fortification or dietary plan) for infants, children,
MMN supplementation was assessed in three reviews (Bhutta adults and pregnant women (Silva Neto 2019). In Tay 2015, the
2012; Haider 2011; Keats 2019). Trials included in Bhutta 2012 included trials assessed the effect of two to three times daily iron
assessed the effect of MMN supplementation using the United supplementation of 200 mg ferrous sulphate for elderly people after
Nations International Multiple Micronutrient Antenatal Preparation hip or knee arthroplasty for a duration of four to six weeks. Tolkien
(UNIMMAP) formulation at least six days a week, starting at 28 2015 also investigated the effects of daily iron supplementation (20
weeks' gestation at the latest, and lasting until delivery. Das mg/day to 222 mg/day ferrous sulphate) versus placebo or daily
2018 included trials assessed daily LNS with 118 kcal/day or 372 iron supplementation (100 mg/day to 400 mg/day ferrous sulphate)
kcal/day. Haider 2011 investigated daily MMN supplementation versus IV iron for adults; the interventions lasted for 1 week up to
interventions using UNIMMAP or comparable formulations, starting 26 weeks.
at any gestational week and for any length. Keats 2019 included
trials on daily supplementation of MMN with iron and folic Twelve reviews assessed fortification interventions (Das 2019b;
acid, starting from enrolment (any trimester) and lasting until Field 2020; Finkelstein 2019; Garcia-Casal 2018; Gera 2012; Hess
(Review)
Informed decisions.
2016; Huo 2015; Peña-Rosas 2019; Ramírez-Luzuriaga 2018; Sadighi 2011; De-Regil 2017; Eichler 2019; Low 2013; Mayo-Wilson 2014a;
2019; Tablante 2019; Yadav 2019). Garcia-Casal 2018 assessed the Thompson 2013). Aaron 2015 assessed trial quality by publication
effects of iron fortification of maize flour on anaemia and iron status bias, method of randomisation, type of blinding, the percentage
in the general population using 2.8 mg to 5.6 mg elemental iron of loss to follow-up and subgroup analyses. Das 2013a assessed
per 100 g flour, 9.8 mg reduced iron per 100 g flour, or 42.4 mg bias using the following domains: sequence allocation, allocation
ferrous fumerate per 100 g flour for 6 to 10 months. Gera 2012 concealment, blinding, incomplete outcome data addressed and
included trials looking at the effect of daily or intermittent iron selective reporting. Six reviews performed GRADE assessment for
fortification in individuals, families or communities using mainly one or more of our primary and secondary outcomes (Aaron 2015;
less than 10 mg of ferrous sulphate for up to 12 months. Hess 2016 De-Regil 2011; De-Regil 2017; Eichler 2019; Mayo-Wilson 2014a;
assessed micronutrient-fortified condiments or noodle products Thompson 2013). Two reviews did not perform GRADE assessment
using various iron doses in children and adults with a follow-up (Das 2013a; Low 2013).
period of 2.4 months to 2 years. In Huo 2015, the included trials
assessed the effect of sodium iron ethylenediaminetetraacetate Adolescent children (aged 11 to 18 years)
(NaFeEDTA)-fortified soy sauce in any population in which anaemia All four reviews used the Cochrane RoB 1 tool (Higgins 2011)
was a public health problem, with iron doses in NaFeEDTA ranging to assess the methodological quality of the included trials
from 2.3 mg/day/person to 20 mg/day/person for an intervention (Fernández-Gaxiola 2019; Neuberger 2016; Salam 2016; Salam
period of 3 to 18 months. Another review assessed double-fortified 2020). Three reviews performed GRADE assessment for one or more
salt with elemental iron doses of 1 mg to 3 mg using mostly of our primary and secondary outcomes (Fernández-Gaxiola 2019;
ferrous sulphate, ferrous fumarate and ferric pyrophosphate, for Salam 2016; Salam 2020). Neuberger 2016 did not perform GRADE
up to six months in any participant (Ramírez-Luzuriaga 2018). One assessment.
review focused on improving dietary diversity and quality through
increasing the daily consumption or use of food prepared in iron Non-pregnant women of reproductive age (aged 19 to 49 years)
or aluminium pots with the intervention lasting 5 to 12 months
(Geerligs 2003). Four reviews used the Cochrane RoB 1 tool (Higgins 2011) to
assess the methodological quality of the included trials (Abe
Methodological quality of included reviews 2016; Houston 2018; Low 2016; Sultan 2019). Lassi 2020 used the
Cochrane RoB 1 tool (Higgins 2011) and EPOC criteria (EPOC 2019).
Quality of the evidence in included reviews Low 2016 and Lassi 2020 performed GRADE assessment for our
Below, we summarise the risk of bias assessment of the included primary and secondary outcomes. Abe 2016 intended to do GRADE
trials and the GRADE assessment of the certainty of the evidence in assessment but was not able to due to the lack of outcomes.
the included reviews. Further details can be found in Table 3, Table Houston 2018 and Sultan 2019 did not perform GRADE assessment.
4, Table 5, Table 6, Table 7 and Table 8.
Pregnant women of reproductive age (aged 15 to 49 years)
Infants (aged 6 to 23 months) Nineteen reviews used the Cochrane RoB 1 tool (Higgins 2011)
Seven reviews used the Cochrane RoB 1 tool (Higgins 2011) to to assess the methodological quality of the included trials (Abu
assess the methodological quality of the included trials (Abdullah Hashim 2017; Bhutta 2012; Buppasiri 2015; Das 2018; De-Regil
2013; Das 2019a; Eichler 2012; Kristjansson 2015; Matsuyama 2017; 2015; Govindappagari 2019; Haider 2011; Keats 2019; Lassi 2013;
Pasricha 2013; Suchdev 2020). Dekker 2010 used the Jadad level- McCauley 2015; Peña-Rosas 2015a; Peña-Rosas 2015b; Qassim
of-evidence score for RCTs (Jadad 1996), whereas Pratt 2015 used 2018; Qassim 2019; Radhika 2019; Reveiz 2011; Rumbold 2015; Shi
a Modified Critical Appraisal Skills Programme (CASP) tool (CASP 2015; Suchdev 2015). Daru 2016 used the Jadad method for quality
2013). In Petry 2016b, the methodological quality of the trials assessment (Jadad 1996). Haider 2013 assessed trial quality using
was based on the assessment of random sequence generation, the following domains: randomisation technique, concealment of
adequacy of blinding of trial participants and personnel and allocation, blinding and loss to follow-up. Imdad 2012 only used the
completeness of outcomes assessment. In Salam 2013, each GRADE tool to assess trial limitations. Thorne-Lyman 2012 assessed
trial was assessed and graded according to the Child Health trial bias using a modified version of the CHERG's GRADE tool
Epidemiology Reference Group's (CHERG) adaptation of the GRADE (Walker 2010). Twelve reviews performed GRADE assessment for
technique (Walker 2010). Dewey 2009 did not describe the tool one or more of our primary and secondary outcomes (Abu Hashim
used for quality assessment. Shapiro 2019 used the National Heart, 2017; Bhutta 2012; Das 2018; Haider 2011; Imdad 2012; McCauley
Lung and Blood Institute (NHLBI) Quality Assessment of Controlled 2015; Peña-Rosas 2015a; Peña-Rosas 2015b; Qassim 2019; Radhika
Intervention Studies for RCTs, and the NHLBI Quality Assessment 2019; Suchdev 2015; Thorne-Lyman 2012). Eleven reviews did not
Tool for Observational Cohort and Cross-Sectional Studies (NHLBI). perform GRADE assessment (Buppasiri 2015; Daru 2016; De-Regil
Four reviews performed GRADE assessment for one or more of 2015; Govindappagari 2019; Haider 2013; Keats 2019; Lassi 2013;
our primary and secondary outcomes (Das 2019a; Petry 2016b; Qassim 2018; Reveiz 2011; Rumbold 2015; Shi 2015).
Salam 2013; Suchdev 2020). Nine reviews did not perform GRADE
assessment (Abdullah 2013; Dekker 2010; Dewey 2009; Eichler 2012;
Kristjansson 2015; Matsuyama 2017; Pasricha 2013; Pratt 2015; Twelve reviews used the Cochrane RoB 1 tool (Higgins 2011) to
Shapiro 2019). assess the methodological quality of the included trials (Arabi
2020; Basutkar 2019; Field 2020; Finkelstein 2019; Gera 2012; Huo
Preschool and school-aged children (aged 2 to 10 years) 2015; Silva Neto 2019; Smelt 2018; Tablante 2019; Tay 2015; Tolkien
Six reviews used the Cochrane RoB 1 tool (Higgins 2011) to 2015; Yadav 2019), and three reviews (Garcia-Casal 2018; Peña-
assess the methodological quality of the included trials (De-Regil Rosas 2019; Sadighi 2019) used Cochrane EPOC's risk of bias tool
(Review)
Informed decisions.
(EPOC 2019). Das 2019b applied the Cochrane RoB 1 tool for review assessed the effect and safety of oral iron supplementation
RCTs (Higgins 2011) and Cochrane EPOC's risk of bias tool for alone or in combination with co-interventions versus control or
non-RCTs and CBA studies (EPOC 2019). Casgrain 2012 used a co-intervention alone (dose: 12.5 mg or less, 12.6 mg to 30 mg,
scale designed by the EURopean micronutrient RECommendations 31 mg to 59 mg, > 60 mg; frequency: per day). The outcomes
Aligned (EURRECA) Network of Excellence (on the basis of Cochrane related to anaemia informed guidelines for anaemia control: Hb (g/
methods) to assess trial quality (Higgins 2011). Gera 2007a and L), anaemia, IDA, and safety. IDA was defined by trial investigators
Gera 2009 assessed the methodological quality (A, B, C or D) using and ID diagnosed with an adverse effect (any side effects, vomiting,
the following domains: randomisations, allocation concealment, diarrhoea, constipation). Twenty-six RCTs assessed the effects of
follow-up and blinding. In Geerligs 2003, the Delphi list was used this intervention on Hb level and reported iron supplementation
as a mean for quality assessment (Verhagen 1998). Hess 2016 increased Hb level (mean difference (MD) 7.22 g/L, 95% confidence
used the CRD Guidance for Undertaking Reviews in Health Care interval (CI) 4.87 to 9.57; 5479 infants; GRADE: not assessed).
(CDR 2009) and assessed risk of bias using the following domains: Seventeen RCTs assessed the effects of iron supplementation
adequate sequence generation, allocation concealment, blinding, on anaemia and reported that this intervention decreased the
incomplete outcome data addressed, and no selective reporting. incidence of anaemia (risk ratio (RR) 0.61, 95% CI 0.50 to 0.74;
Ramírez-Luzuriaga 2018 used the Effective Public Health Practice 4825 infants; GRADE: not assessed). The intervention reduced the
Project (EPHPP) quality assessment tool (Jackson 2005). In this incidence of IDA (RR 0.14, 95% CI 0.10 to 0.22; 6 RCTs, 2145 infants;
category, only six reviews performed GRADE assessment (Basutkar GRADE: not assessed) and ID (RR 0.30, 95% CI 0.15 to 0.60; 9 RCTs,
2019; Das 2019b; Field 2020; Garcia-Casal 2018; Peña-Rosas 2019; 2464 infants; GRADE: not assessed). Regarding adverse effects, daily
Tablante 2019). oral iron supplementation increased vomiting (RR 1.38, 95% CI 1.10
to 1.73; 3 RCTs, 1020 infants), but there was no clear evidence of an
Quality of included reviews effect on other adverse effects: "any side-effects" (RR 1.10, 95% CI
We assessed the methodological quality of the reviews using 0.98 to 1.25; 3 RCTs, 912 infants), diarrhoea (prevalence) (RR 1.03,
AMSTAR (Shea 2007a; Shea 2007b; Shea 2009). Some reviews had 95% CI 0.86 to 1.23; 6 RCTs, 1697 infants), diarrhoea (incidence) (RR
specific methodological limitations that could create bias: conflict 0.98, 95% CI 0.88 to 1.09; 5 trials), and constipation (RR 0.54, 95% CI
of interest disclosure not stated (56 reviews), publication bias not 0.05 to 5.83; 2 trials, 570 infants).
assessed (38 reviews), included and excluded trials not listed (35 Iron supplementation versus control or other intervention to increase
reviews), and review protocol not provided (21 reviews). Hb status and reduce the prevalence of ID and IDA
We summarise the assessment of the methodological quality of the Eight RCTs and cluster-RCTs comprising 8109 children aged 6
included reviews in Table 15; Table 16; Table 17; Table 18; Table 19 months to 36 months, more than 60% of whom were under
and Table 20. the age of two years, were included in this review (Pratt 2015).
This review assessed the effects on several strategies or methods
Effect of interventions used to reduce the prevalence of ID and IDA. ID was defined by
trialists, based on biomarker of iron status, for example, ferritin <
Infants (aged 6 to 23 months) (13 reviews)
12 μg/L for preschool-aged children. The outcomes Hb, anaemia
Thirteen systematic reviews assessed interventions to prevent and ID were reported. Only one RCT reported that daily 12.5
or control anaemia in infants aged 6 months to 23 months mg iron supplementation resulted in higher Hb levels compared
(Abdullah 2013; Das 2019a; Dekker 2010; Dewey 2009; Eichler 2012; with control (P = 0.046, 391 infants). However, there was no clear
Kristjansson 2015; Matsuyama 2017; Pasricha 2013; Petry 2016b; evidence of difference for the group receiving iron supplements
Pratt 2015; Salam 2013; Shapiro 2019; Suchdev 2020). GRADE weekly. Two RCTs (675 children) reported on anaemia and in
assessments were provided in four out of 13 reviews. The effects of one RCT, 21% of infants were anaemic at nine months; however,
the interventions are summarised in Table 21. there was no clear evidence of a difference in anaemia prevalence
between the groups for the occurrence of anaemia. The second
Supplementation (6 reviews) RCT reported a dose-response effect in the group receiving daily
Six systematic reviews assessed supplementation interventions for supplements, but not in the group receiving weekly iron. At nine
infants aged 6 months to 23 months (Abdullah 2013; Das 2019a; months, although 81% of infants had ID, there was no clear
Dekker 2010; Pasricha 2013; Petry 2016b; Pratt 2015). Four reviews evidence of a difference between groups for the occurrence of ID (1
addressed prevention (Das 2019a; Pasricha 2013; Petry 2016b; Pratt RCT, 284 infants). Comparing the efficiency of different strategies,
2015), and two treatment (Abdullah 2013; Dekker 2010). See Table Hb levels increased in all treatments, and anaemia prevalence
21. reduced more in the MMN supplement group (72%) and iron
and folic acid supplementation group (69%) than complementary
Iron supplementation fortified food (45%) (1 RCT, 2666 children).
Four reviews assessed iron supplementation in infants aged 6 Daily iron administration versus control
months to 23 months (Abdullah 2013; Pasricha 2013; Petry 2016b;
Pratt 2015). In total, 90 trials were included in one systematic review assessing
the effect of iron and zinc supplementation (Petry 2016b). Thirty-
Prevention three RCTs, cluster-RCTs, and quasi-RCTs comprising 7772 infants
Oral iron supplementation alone or with co-intervention versus
assessed the effects of iron supplementation. Additionally, 47
control or co-intervention RCTs, cluster-RCTs, and quasi-RCTs assessed the effects of zinc
supplementation on children aged 6 months to 23 months. This
One systematic review included 33 RCTs randomising 42,015 review assessed the effects of iron supplementation on Hb,
healthy infants aged 4 months to 23 months (Pasricha 2013). This
(Review)
Informed decisions.
anaemia, IDA, ID, and safety (dose: ≤ 15 mg/day). IDA was defined Fortification (6 reviews)
as Hb < 105 g/L or < 110 g/L and serum ferritin < 10 μg/L or
Six systematic reviews assessed fortification interventions for
< 12 μg/L. ID was defined as serum ferritin < 10 μg/L or < 12
infants 6 months to 23 months (Dewey 2009; Eichler 2012;
μg/L. Daily iron supplementation increased Hb concentrations for
Matsuyama 2017; Pratt 2015; Salam 2013; Suchdev 2020).
infants compared with control (MD 4.10 g/L, 95% CI 2.80 to 5.30; 30
trials, 6569 infants; moderate-certainty evidence). This intervention Five reviews focused on prevention (Eichler 2012; Matsuyama 2017;
decreased anaemia (RR 0.59, 95% CI 0.49 to 0.70; 22 trials, 5647 Pratt 2015; Salam 2013; Suchdev 2020), and one on prevention and
infants; low-certainty evidence), IDA (RR 0.20, 95% CI 0.11 to 0.37; 8 treatment (Dewey 2009). See Table 21.
RCTs, 3464 infants; high-certainty evidence), and ID (RR 0.22, 95% CI
0.14 to 0.35; 13 trials, 3698 infants; high-certainty evidence). There Prevention
was no clear evidence of a difference in the incidence of diarrhoea
Two reviews assessed iron fortification in infants aged 6 months to
between the intervention and control group (8 trials).
23 months (Eichler 2012; Pratt 2015).
Treatment
Iron-fortified milk versus control
Oral iron therapy versus placebo or no treatment
Eight RCTs and cluster-RCTs comprised 8109 children aged 6
Two RCTs comprising 249 non-anaemic, iron-deficient infants and months to 36 months and under two years, and of whom, over
children aged 6 months to 30 months (mean age 17 months) 60% were included in this review (Pratt 2015). This review assessed
were included in this systematic review (Abdullah 2013). This the effects of several strategies or methods used to reduce the
review assessed the effects of iron supplementation (dose: ≥ 2 mg prevalence of ID and IDA and the outcomes of Hb and anaemia
elemental Fe/kg body weight; frequency: per day administered for prevalence were reported. ID was defined by trialists, based on
≥ 3 months) compared with placebo or no treatment for children's biomarker of iron status, for example, ferritin < 12 μg/L for
outcomes: mental and psychomotor development. Due to high preschool-aged children. Hb levels in infants receiving iron-fortified
heterogeneity between the two trials, post-treatment results were milk versus control were positively associated with the treatment
reported separately. In one trial, iron supplementation increased (P < 0.001, 1 trial, 115 children; GRADE: not assessed). Two RCTs
Hb level (MD 11.50 g/L, 95% CI 5.10 to 17.90; 28 children; GRADE: reported on anaemia prevalence (2 trials, 910 children; GRADE: not
not assessed). The second trial reported no clear evidence between assessed). One RCT reported a decline from 41.4% to 12.1% in the
intervention and control group (MD 2.70 g/L, 95% CI −1.70 to 7.10; intervention group and no decline in the control group, and one
40 children; GRADE: not assessed). RCT reported a decline in anaemia prevalence from baseline to 6
months and 12 months (intervention group: 44.5% to 12.7% to 4.0%
Prevention
and control group: 42.6% to 19.7% to 9.4%).
Seventeen trials comprising 23,200 children aged 6 months to
Iron-fortified milk and cereals versus non-fortified food
23 months were included in this review (Das 2019a). This review
assessed the effects of LNS plus complementary feeding compared Eighteen RCTs and cluster-RCTs comprising 5468 children aged
with no intervention, and LNS plus complementary feeding six months to five years (mean age = 6 months to 23 months at
compared with micronutrient powders (MNPs). inclusion) were included in this review (Eichler 2012). This review
assessed the effects on micronutrient-fortified milk or cereals on Hb
LNS plus complementary feeding versus no intervention
and anaemia. Iron-fortified milk or cereals increased Hb levels (MD
LNS plus complementary feeding reduced the risk of anaemia by 6.20 g/L, 95% CI 3.40 to 8.90; 13 trials, 2274 children; GRADE: not
21% (RR 0.79, 95% CI 0.69 to 0.90; 5 trials, 2332 children; low- assessed) and reduced anaemia (RR 0.50, 95% CI 0.33 to 0.75; 11
certainty evidence). There was no clear evidence of a difference in trials, 3100 children; GRADE: not assessed) compared with placebo
the adverse effects between the groups (RR 0.86, 95% CI 0.74 to or no intervention.
1.01; 3 trials, 3382 children; low-certainty evidence).
Prevention
LNS plus complementary feeding versus MNP
Three reviews assessed MNP interventions in infants 6 months to
There was a reduction in the risk of anaemia for children receiving 23 months (Suchdev 2020; Pratt 2015; Salam 2013).
LNS plus complementary feeding compared with MNP (RR 0.38,
MNP, including at least iron, zinc and vitamin A versus placebo or no
95% CI 0.21 to 0.68; 2 trials, 557 children; low-certainty evidence).
intervention, or iron supplementation
Treatment Eight RCTs comprising 3748 children aged 6 months to 23
Zinc supplementation versus placebo months were included in this review (Suchdev 2020). This
review assessed the effects and the safety of MNP on Hb,
Twenty-one RCTs randomising 3869 children aged 0 to 15 years anaemia prevalence, and ID (ID was defined by trialists) and
were included in this review (Dekker 2010). Although the mean age compared the intervention with placebo or no intervention, or iron
at baseline was 32 months, the majority of the trials commenced supplementation. MNP, including at least iron, zinc and vitamin A
between 6 months to 23 months. This review assessed the effect increased Hb concentration (MD 5.87, 95% CI 3.25 to 8.49; 6 RCTs,
of zinc supplementation (dose: 10 mg or 20 mg zinc; frequency: 1447 children; moderate-certainty evidence), reduced anaemia (RR
per day) compared with no treatment or placebo. The intervention 0.69, 95% CI 0.60 to 0.78; 6 trials, 1447 children; moderate-certainty
showed no clear evidence of a difference in Hb levels between evidence), reduced ID (RR 0.49, 95% CI 0.35 to 0.67; 4 trials 586
intervention and control groups (weighted mean difference (WMD) children; high-certainty evidence) compared with placebo or no
0.79 g/L, 95% CI −0.62 to 2.21; 21 trials, 3869 children; GRADE not intervention, but no clear evidence of a difference was seen in
assessed).
(Review)
Informed decisions.
diarrhoea between groups (RR 1.33, 95% CI 1.00 to 1.78; 206 Prevention and treatment
children). Home fortification of complementary foods versus iron drops or
placebo or no intervention
There was no difference between the MNP intervention group and
the iron supplementation group on Hb levels (MD −2.36 g/L, 95% Fourteen RCTs, cluster-RCTs and two non-RCTs comprising 6113
CI −10.30 to 5.58; 2 trials, 278 children; low-certainty evidence) infants and children aged four months to 36 months were included
and anaemia (RR 0.89, 95% CI 0.58 to 1.39; 1 trial, 145 children; in this review (Dewey 2009). This review assessed the effects and
low-certainty evidence). This intervention reduced the incidence safety of home fortification on Hb, anaemia, ID, and diarrhoea. ID
of diarrhoea (RR 0.52, 95% CI 0.38 to 0.72; 1 trial, 262 children), was defined as ferritin < 12 μg/L. The intervention was compared
the incidence of vomiting (RR 0.58, 95% CI 0.35 to 0.95; 1 trial, with iron drops or placebo or no intervention. There was no
262 children), the incidence of staining of teeth (RR 0.37, 95% clear evidence of a difference between home fortification of
CI 0.16 to 0.82; 2 trials, 395 children), and the incidence of stool complementary foods and iron drops on Hb levels (MD -0.91, 95%
discolouration (RR 0.80, 95% CI 0.66 to 0.98; 2 trials, 395 children) CI -11.96 to 10.14; 3 trials, 1263 children), anaemia (RR 1.04, 95% CI
compared with iron supplementation. 0.76 to 1.41; 3 trials, 1263 children) and diarrhoea (SMD -0.34, 95%
CI -0.71 to 0.03; 2 trials, 808 children).
MNP versus no intervention or control
Home fortification of complementary foods compared with
Seventeen RCTs comprising children aged 6 months to 11 years
placebo or no intervention increased Hb levels (MD 5.06 g/L, 95% CI
(majority conducted in infants 6 to 23 months) were included in this
2.29 to 7.83; 8 RCTs, 2649 children), reduced anaemia (RR 0.54, 95%
review (Salam 2013). This review assessed the effects and safety of
CI 0.46 to 0.64; 8 trials, 4331 children), reduced ID (RR 0.44, 95% CI
MNP on Hb, anaemia prevalence, ID, and the incidence of diarrhoea.
0.22 to 0.86; 3 trials, 1210 children), but resulted in no difference in
MNP versus control or no intervention increased Hb concentration
the incidence of diarrhoea between intervention and control group
(standardised mean difference (SMD) 0.98, 95% CI 0.55 to 1.40;
(RR 1.07, 95% CI 0.78 to 1.47; 5 trials, 1195 children).
14 trials, 9132 children; moderate-certainty evidence), reduced
anaemia (RR 0.66, 95% CI 0.57 to 0.77; 11 trials, 2524 children; Improving dietary diversity and quality (3 reviews)
moderate-certainty evidence), reduced IDA (RR 0.43, 95% CI 0.35
to 0.52; 7 trials, 1390 children; moderate-certainty evidence), but Three systematic reviews assessed preventive interventions to
increased the incidence of diarrhoea (RR 1.04, 95% CI 1.01 to 1.06; improve dietary diversity and quality for infants 6 months to 23
4 trials, 3371 children; moderate-certainty evidence). There was months (Kristjansson 2015; Pratt 2015; Shapiro 2019). See Table 21.
no clear evidence of a difference between groups for the outcome
Prevention
recurrent diarrhoea (RR 2.86, 95% CI 0.12 to 69.0, 1 trial; moderate-
certainty evidence). Food-based strategies: red meat, fortified cow's milk versus control
Mironutrient sprinkles versus control One RCT (225 children) assessed the effects of food-based
strategies: red meat and fortified cow's milk versus control and
Two RCTs (3633 children) assessed the effects of micronutrient found no evidence of a difference in Hb levels between intervention
sprinkles versus control and reported results on Hb levels and control group (Pratt 2015).
separately (Pratt 2015). One trial reported that Hb levels increased
in the intervention group compared with the control group from Caterpillar cereal versus usual diet
baseline to 12 to 18 months (6.10 g/L intervention group versus
One RCT (175 children) assessed the effects of caterpillar cereal
2.20 g/L control group, P < 0.001; 2 trials, 3633 children; GRADE: not
compared with usual diet. This review showed that caterpillar
assessed). The second trial reported that Hb levels increased in the
cereal increased Hb levels (mean (SD) caterpillar cereal: 10.70 g/dL
intervention group compared with the control group from baseline
(1.6), usual diet: 10.10 g/dL (1.8) (P < 0.05); GRADE: not assessed)
to two months (7.00 g/L intervention group versus 2.00 g/L control
and reduced IDA prevalence (caterpillar cereal: 26%, usual diet:
group).
50% (P < 0.01); GRADE: not assessed) (Shapiro 2019).
Prevention
Beef versus fortified rice-soy cereal
Fortified milk versus control milk (cow's milk or non- or low-fortified
milk) One RCT (1602 children) evaluated the effects of beef compared
with fortified rice-soy cereal. This review showed no evidence of a
Fifteen RCTs including individual RCTs and cluster-RCTs comprising difference in Hb levels (Shapiro 2019).
children (mean age at baseline was 6 months to 22.4 months) were
included in this review (Matsuyama 2017). This review assessed Food fortified with fish powder versus food with or without vitamins
the effects of fortified milk (dose: not reported; frequency: not and minerals
reported) on Hb and anaemia compared with cow's milk or non- One RCT (190 children) assessed the effects of food fortified with
or low-fortified milk. There was no clear evidence of a difference fish powder compared with food with or without vitamins and
between fortified milk and control milk on Hb level (MD 5.89, 95% minerals. They found no evidence of a difference in HB levels
CI −0.24 to 12.02; 9 trials, number of participants: not reported; (Shapiro 2019).
GRADE assessment: not assessed). While fortified milk reduced
anaemia (odds ratio (OR) 0.32, 95% CI 0.15 to 0.66; 9 trials, number Prevention
of participants: not reported; GRADE assessment: not assessed).
Twenty-one RCTs and 11 controlled before-after (CBA) trials
compromising children aged three months to five years (60%
of the trials included children under 2 years of age) were
included (Kristjansson 2015). This review assessed the effects
(Review)
Informed decisions.
of supplementary feeding alone or in combination with added day to 10 mg/kg/day; frequency: daily), a commonly used strategy
micronutrient on Hb concentration and anaemia. Supplementary to combat anaemia in primary school-aged children. They did not
feeding was associated with an increase in Hb levels (change in Hb report the definition of IDA and ID. Iron supplementation compared
levels: SMD 0.49, 95% CI 0.07 to 0.91; 5 trials, 300 children; GRADE: to placebo or control resulted in an increase in Hb concentration
not assessed). The review included no results for anaemia. (MD 8.38 g/L, 95% CI 6.21 to 10.56; 28 trials, 6545 children; GRADE:
not assessed) and a reduction in anaemia (RR 0.50, 95% CI 0.39
Preschool and school-aged children (aged 2 to 10 years) (8 to 0.64; 7 trials, 1763 children; GRADE: not assessed), reduction in
reviews) IDA (RR 0.12, 95% CI 0.02 to 0.66; 2 trials, 334 children; GRADE: not
Eight systematic reviews assessed interventions to prevent or assessed), and reduction in ID (RR 0.21, 95% CI 0.07 to 0.63; 4 trials,
control anaemia in preschool and school-aged children aged 2 to 10 1020 children). There was no evidence of a difference in adverse
years (Aaron 2015; Das 2013a; De-Regil 2011; De-Regil 2017; Eichler events of gastrointestinal upset (RR 1.30, 95% CI 0.89 to 1.91; 4
2019; Low 2013; Mayo-Wilson 2014a; Thompson 2013). GRADE trials, 576 children), constipation (RR 3.44, 95% CI 0.66 to 19.68;
assessments were provided in six out of eight reviews. The effects 2 trials, 202 children) and vomiting (RR 0.86, 95% CI 0.13 to 5.67;
of interventions are summarised in Table 22. 2 trials, 202 children) for children receiving iron supplementation
compared with those receiving placebo or control.
Supplementation (4 reviews)
Intermittent iron supplementation
Four systematic reviews assessed supplementation interventions
Thirty-three RCTs, cluster-RCTs and quasi-RCTs comprising 13,114
for preschool and school-aged children aged 2 to 10 years (De-
children under 12 years of age were included in the systematic
Regil 2011; Low 2013; Mayo-Wilson 2014a; Thompson 2013).
review by De-Regil 2011. The review assessed the effects of
See Table 22. One was a prevention (Mayo-Wilson 2014a), and three
intermittent iron supplementation (dose: 7.5 mg/week to 200 mg/
were prevention or treatment reviews (De-Regil 2011; Low 2013;
week; frequency: twice, 3 times or once a week), alone or in
Thompson 2013).
combination with other vitamins and minerals, on nutritional and
Prevention developmental outcomes in children from birth to 12 years of age
compared with placebo, no intervention or daily supplementation.
Zinc versus no zinc or zinc plus iron
IDA was defined by the presence of anaemia and ID, diagnosed
Eighty RCTs, cluster-RCTs and cross-over RCTs randomising over with an indicator of iron stats selected by trialists. Trialists
205,401 children aged 6 months to 12 years of age were included measured ID by using indicators of iron status, such as ferritin
in the Mayo-Wilson 2014a systematic review, which assessed the or transferrin. An increase in Hb concentration was seen for
effects of zinc supplementation (dose: < 5 mg to 20 mg daily; children receiving intermittent supplementation with iron alone
frequency: from daily to weekly) versus no zinc or zinc plus iron or with other nutrients compared to placebo or no intervention
for preventing mortality and morbidity, and for promoting growth. (MD 5.20 g/L, 95 % CI 2.51 to 7.88; 19 trials, 3032 children;
They did not report the definition of ID. An increase in vomiting low-certainty evidence). There was a reduction in anaemia (RR
episodes (RR 1.68, 95% CI 1.61 to 1.75; 5 trials, 4095 children) and 0.51, 95 % CI 0.37 to 0.72; 10 trials, 1824 children; moderate-
in ≥ 1 vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 trials, 35,192 certainty evidence) and ID (RR 0.24, 95 % CI 0.06 to 0.91; 3 trials,
children; high-certainty evidence) was found for children receiving 431 children; very low-certainty evidence) for children receiving
zinc compared to those not receiving zinc. There was no evidence intermittent iron supplementation compared with those receiving
of a difference in blood Hb concentration (SMD 0.05, 95% CI -0.00 placebo or no intervention. In one trial, there was no evidence
to 0.10; 26 trials, 6024 children; GRADE: not assessed), prevalence of a difference in any side effects between the intervention and
of anaemia (RR 1.00, 95% CI 0.95 to 1.06; 13 trials, 4287 children; control groups (RR 3.87, 95% CI 0.19 to 76.92; 53 children). For
GRADE: not assessed), prevalence of ID (RR 0.99, 95% CI 0.89 to 1.10; children receiving intermittent iron supplementation compared
10 trials, 3149 children), and ≥ 1 side effect (RR 1.13, 95% CI 1.00 with children receiving daily iron supplementation, no difference
to 1.27; 3 trials, 850 children) between the intervention and control was seen in Hb concentration (MD −0.60 g/L, 95% CI −1.54 to 0.35;
groups. There was an increase in blood Hb concentration (SMD 19 trials, 2851 children; low-certainty evidence), diarrhoea (RR 1.17,
−0.23, 95% CI −0.34 to −0.12; 8 trials, 1341 children; GRADE: not 95% CI 0.60 to 2.28; 2 trials, 122 children), and any side effects (RR
assessed) and a reduction in the prevalence of anaemia (RR 0.78, 0.60, 95% CI 0.19 to 1.87; 4 trials, 895 children). However, there was
95% CI 0.67 to 0.92; 3 trials, 482 children; GRADE: not assessed), an increase in anaemia (RR 1.23, 95% CI 1.04 to 1.47; 6 trials, 980
and the prevalence of ID (RR 0.12, 95% CI 0.04 to 0.32; 2 trials, 248 children; low-certainty evidence) and ID (RR 4.00, 95% CI 1.23 to
children) for children receiving zinc plus iron compared to those 13.05; 1 trial, 76 children; very low-certainty evidence) for children
receiving zinc alone. receiving intermittent iron supplementation compared to those
receiving daily iron supplementation.
Prevention or treatment
Oral iron supplementation
Three reviews assessed iron supplementation in preschool and
school-aged children aged 2 to 10 years (De-Regil 2011; Low 2013; Fifteen RCTs and cluster-RCTs were included in the Thompson
Thompson 2013). 2013 review, which summarised the evidence for effects of daily
iron supplementation (dose: 5 mg/day to 50 mg/day; frequency:
Daily iron supplementation versus placebo or control at least 5 days per week) administered to children aged two
Thirty-two RCTs and cluster-RCTs randomising over 7089 primary to five years. In this systematic review, nine trials reported Hb
school children aged 5 to 12 years were included in the Low concentration and found an increase in Hb concentration for
2013 systematic review. This review evaluated the effects of daily children receiving iron supplementation compared to the control
iron supplementation (dose: 5 mg/day to 400 mg/day or 3 mg/kg/ group (MD 6.97 g/L, 95% CI 4.21 to 9.72; 9 trials, 1690 children;
(Review)
Informed decisions.
high-certainty evidence). In one trial, the intervention showed no Prevention

clear evidence of a difference in reducing anaemia compared to the Point-of-use fortification of foods with MNP versus no intervention or
control group (79% anaemic in the iron group versus 81% anaemic placebo
in the control group; very low-certainty evidence).
Thirteen RCTs, quasi-RCTs, and cluster-RCTs randomising 5810
Fortification (4 reviews) children aged 24 to 59 months and children aged 5 to 12 years
receiving point-of-use fortification of foods with MNP were included
Four systematic reviews assessed fortification interventions for in this review (De-Regil 2017). The review assessed the effects of
preschool and school-aged children aged 2 to 10 years (Aaron 2015; point-of-use fortification of foods with iron-containing MNP alone,
Das 2013a; De-Regil 2017; Eichler 2019; see Table 22). All systematic or in combination with other vitamins and minerals (dose: not
reviews focused on prevention. reported; frequency: daily), on nutrition, health and development
Prevention among children of preschool (24 to 59 months) and school age (5
to 12 years). IDA was defined by the presence of anaemia and ID,
MMN-fortified beverages versus control diagnosed with an indicator of iron status as selected by trialists. ID
Ten RCTs randomising over 4645 apparently healthy school-aged was defined as ferritin concentrations less than 15 μg/L. Point-of-
children and women of reproductive age were included in the use fortification of foods with MNP increased Hb concentration (MD
review by Aaron 2015, which evaluated the nutritional impacts of 3.37 g/L, 95% CI 0.94 to 5.80; 11 trials, 2746 children; low-certainty
MMN-fortified beverages (dose: not reported; frequency: daily) in evidence) and reduced the prevalence of anaemia (RR 0.66, 95% CI
the context of low-middle-income countries. They defined ID as 0.49 to 0.88; 10 trials, 2448 children; moderate-certainty evidence),
ferritin levels less than 27 pmol/L to 45 pmol/L and IDA as Hb less and ID (RR 0.35, 95% CI 0.27 to 0.47; 5 trials, 1364 children;
than 110 g/L to 120 g/L and ferritin levels less than 27 pmol/L to moderate-certainty evidence) compared with no intervention or
45 pmol/L. They found an increase in Hb concentration (MD 2.76 g/ placebo. No evidence of a difference was seen between the groups
L, 95% CI 1.19 to 4.33; 8 trials, 3835 children; moderate-certainty for IDA (RR 0.28, 95% CI 0.07 to 1.10; 3 trials, 918 children; GRADE:
evidence) and a reduction in anaemia (RR 0.63, 95% CI 0.54 to not assessed), adverse events (RR 1.09, 95% CI 0.16 to 7.42; 1 trial,
0.73; 6 trials, 2828 children; moderate-certainty evidence), ID (RR 90 children; moderate-certainty evidence) and diarrhoea (RR 0.97,
0.32, 95% CI 0.23 to 0.45; 7 trials, 2523 children; moderate-certainty 95% CI 0.53 to 1.78; 2 trials, 366 children; low-certainty evidence).
evidence), and IDA (RR 0.13, 95% CI 0.07 to 0.25; 3 trials, 1649
Improving dietary diversity and quality
children; low-certainty evidence) when non-dairy MMN-fortified
beverages were compared with control. None of the included reviews assessed interventions to improve
dietary diversity and quality for preschool and school children.
Prevention
Zinc-fortified food versus control (regular diet or unfortified food) Adolescent children (aged 11 to 18 years) (4 reviews)
Eleven RCTs and quasi-RCTs comprising 771 women and children Four systematic reviews assessed interventions to prevent or
(newborn, infants and school-aged children) were included in the control anaemia in adolescent children aged 11 to 18 years
review by Das 2013a. This review investigated the impact of food (Fernández-Gaxiola 2019; Neuberger 2016; Salam 2016; Salam
fortification with zinc (dose: 3.75 mg to 400 mg; frequency: not 2020). GRADE assessments were provided in three out of four
reported) on the health and nutrition of women and children. Only reviews. The effects of the interventions are summarised in Table
one trial reported serum Hb for school-aged children and found 23.
no difference between the intervention and control groups with
regular diet or unfortified foods (SMD 0.28, 95% CI −0.62 to 1.19; 19 Supplementation (4 reviews)
children; GRADE: not assessed). Four systematic reviews assessed iron supplementation for
adolescent children aged 11 to 18 years (Fernández-Gaxiola 2019;
Prevention
Neuberger 2016; Salam 2016; Salam 2020). One review focused on
Centrally-processed fortified dairy products and fortified cereals prevention and three on prevention or treatment (Table 23).
versus non-fortified food
Prevention
Eichler 2019 included 24 studies comprising 9367 children and
adolescents in this review and found no evidence of a difference Iron supplementation with or without folic acid versus placebo/no
supplementation/no fortification
between the centrally-processed fortified dairy products and
fortified cereals (dose: not reported; frequency: not reported) and Salam 2020 assessed the effects of iron supplementation with or
control groups in Hb levels (MD 0.90 g/L, 95% CI -0.10 to 1.80; without folic acid supplementation (dose: not reported; frequency:
14 trials, 4855 children; very low-certainty evidence), incidence of daily and weekly) on the health and nutritional status of
anaemia (RR 0.87, 95% CI 0.76 to 1.01; 12 trials, 1149 children; adolescents aged 10 to 19 years.
very low-certainty evidence), and adverse events (3 trials). While
centrally-processed fortified dairy products reduced the incidence Assessing the effects of daily iron supplementation with or without
of IDA (RR 0.38, 95% CI 0.18 to 0.81; 5 trials, 148 children; very low- folic acid for girls aged 10 to 17 years old, found no evidence
certainty evidence), and incidence of ID (RR 0.62, 95%CI 0.40 to 0.97; of a difference in the incidence of anaemia (RR 1.04, 95% CI
8 trials, 519 children; very low-certainty evidence). 0.88 to 1.24; 1 trial, 1160 children; low-certainty evidence). Also,
comparing weekly iron supplementation with or without folic
acid for girls aged 10 to 17 years old, showed no evidence of
a difference in the incidence of anaemia (RR 1.07, 95% CI 0.91
to 1.26; 1 trial, 1274 children; low-certainty evidence). Four trials
(Review)
Informed decisions.
showed that iron supplementation with or without folic acid CI 4.20 to 9.20 (P < 0.0001); 12 trials, 2462 children; GRADE: not
improved Hb concentrations among adolescents compared with no assessed).
supplementation (MD 0.42 g/L, 95% CI 0.13 to 0.71; 4 trials, 1020
children; low-certainty evidence). 15 trials showed a reduction in the incidence of anaemia for
children (RR 0.63, 95% CI 0.49 to 0.82; 15 trials, 3784 children;
Prevention or treatment GRADE: not assessed).
Intermittent iron supplementation (alone or with any other
micronutrients) versus no supplementation, placebo, or daily iron
Iron plus folic acid supplementation versus placebo
Two reviews assessed iron supplementation (Fernández-Gaxiola
2019; Neuberger 2016). Twenty-five RCTs, quasi-RCTs, and cluster- Neuberger 2016 included six trials comprising 19,456 children living
RCTs comprising 10,996 menstruating women (range = 6 years to in areas with hyperendemic or holoendemic malaria transmission
49 years, but more than 60% of the trials included women under and assessed the effects of iron plus folic acid supplementation
18 years) were included in the Fernández-Gaxiola 2019 systematic compared with placebo or no treatment (mean dose: 2 mg/kg/day;
review. Most trials involved a mix of anaemic and non-anaemic frequency: daily).
women. This review assessed the effects and safety of oral iron
alone or with other vitamins and minerals (dose: 60 mg to 120 One trial showed an increase in Hb concentration (MD 0.90, 95% CI
mg; frequency: once or twice a week) on Hb levels, anaemia, 0.51 to 1.29; 1 trial, 124 children; GRADE: not assessed) and three
IDA, ID and safety. IDA was defined by the presence of anaemia trials showed a reduction in the incidence of anaemia (RR 0.49, 95%
and ID diagnosed with an indicator of iron status selected by CI 0.25 to 0.99; 3 trial, 633 children; GRADE: not assessed).
trialists. ID was defined by trialists using indicators of iron status Prevention or treatment
such as ferritin or transferrin. Fifteen trials assessed the effects
of intermittent iron supplementation alone or with any other Iron supplementation plus antimalarial supplementation versus
micronutrient on Hb level and found an increase in Hb levels (MD placebo
5.19 g/L, 95% CI 3.07 to 7.32; 15 trials, 2886 women; moderate- Neuberger 2016 included four trials comprising 1915 children living
certainty evidence) and decreased the incidence of anaemia (RR in areas with hyperendemic or holoendemic malaria transmission,
0.65, 95% CI 0.49 to 0.87; 11 trials, 3135 women; low-certainty and assessed the effects of iron plus folic acid supplementation
evidence) compared with no supplementation or placebo. There compared with placebo or no treatment (mean dose: 2 mg/kg/day;
was no evidence of a difference in the incidence of IDA (RR 0.07, frequency: daily).
95% CI 0.00 to 1.16; 1 trial, 97 women; low-certainty evidence), ID
(RR 0.50, 95% CI 0.24 to 1.04; 3 trials, 624 women; low-certainty One trial showed that the iron plus antimalarial supplementation
evidence), or any adverse side effect (RR 1.98, 95% CI 0.31 to 12.72; increased in Hb concentration compared with placebo (MD 9.10 g/
3 trials, 630 women; moderate-certainty evidence) between the L, 95% CI 4.70 to 13.50; 1 trial, 151 children; GRADE: not assessed).
intermittent iron supplementation and control groups. Two trials showed a reduction in the incidence of anaemia at the
end of treatment (RR 0.44, 95% CI 0.28 to 0.70; 2 trials, 295 children;
Comparing intermittent iron supplementation (alone or with GRADE: not assessed), and one trial showed a reduction in the
any other micronutrient) versus daily iron supplementation, incidence of anaemia at the end of follow-up (RR 0.37, 95% CI 0.26
intermittent iron supplementation reduced any adverse side effects to 0.54; 1 trial, 420 children; not assessed).
(RR 0.41, 95% CI 0.21 to 0.82; 6 trials, 1166 women; low-certainty
evidence), but there was no difference in Hb levels (MD 0.43 g/ Iron or iron folic acid supplementation alone or in combination with
L, 95% CI −1.44 to 2.31; 10 trials, 2127 women; low-certainty other micronutrient supplementation
evidence), the incidence of anaemia (RR 1.09, 95% CI 0.93 to 1.29; One review assessed iron or iron folic acid supplementation alone
8 trials, 1749 women; moderate-certainty evidence), or ID (RR or in combination with other micronutrient supplementation for
4.30, 95% CI 0.56 to 33.20; 1 trial, 198 women; very low-certainty adolescents (Salam 2016).
evidence).
Thirty-one trials for micronutrient supplementation in an
Iron supplementation versus placebo/no treatment adolescent population (11 to 19 years old) and 10 trials for nutrition
Neuberger 2016 included 31 trials comprising 12,963 children living in pregnant adolescents (13 to 20 years old) were included in this
in areas with hyperendemic or holoendemic malaria transmission, systematic review by Salam 2016. For the adolescent population,
and assessed the effects of iron supplementation compared with most trials included girls, and nine trials included boys and
placebo or no treatment (mean dose: 2 mg/kg/day; frequency: girls. This review assessed the effects of interventions (dose: not
daily). reported; frequency: daily or weekly) on Hb, anaemia, and IDA. They
did not report the definition of IDA.
16 trials for iron supplementation showed an increase in Hb
concentration at the end of treatment for children (MD 7.50 g/L, There was an increase in Hb concentration (MD 1.94 g/L, 95% CI 1.48
95% CI 4.80 to 10.10; 16 trials, 5261 children; GRADE: not assessed), to 2.41, number of participants: not reported; GRADE: not assessed)
for anaemic children (MD 0.95 g/dL, 95% CI 0.38 to 1.51; 7 trials, and reduction in anaemia (RR 0.69, 95% CI 0.62 to 0.76; 11 trials,
2481 anaemic children; GRADE: not assessed), and for non-anaemic 11,861 adolescents; moderate-certainty evidence) for adolescents
children (MD 6.10 g/L, 95% CI 3.80 to 8.50; 9 trials, 2780 non- receiving micronutrient supplementation compared with control.
anaemic children; GRADE not assessed). 12 trials showed that iron
supplementation improved Hb levels at the end of treatment from
baseline compared with no supplementation (MD 6.70 g/L, 95%
(Review)
Informed decisions.
Nutritional supplementation status selected by trialists, ID was measured by trial authors

One review assessed nutritional supplementation for adolescents using indicators of iron status such as ferritin or transferrin. Trials
(Salam 2016). were conducted in numerous countries of differing cultural and
economic backgrounds. Hb concentration increased for women
Prevention or treatment receiving daily oral iron compared to those not receiving daily oral
iron supplementation at the end of therapy (MD 5.30 g/L, 95% CI
Nutritional supplementation and counselling versus control
4.14 to 6.45; 51 trials, 6861 women; high-certainty evidence). At
One trial reported a reduction in IDA for pregnant adolescents the end of therapy, there was a reduction in anaemia (RR 0.39,
receiving nutritional supplementation and counselling compared 95% CI 0.25 to 0.60; 10 trials, 3273 women; moderate-certainty
with control (RR 0.34, 95% CI 0.13 to 0.89; 1 trial, 14 pregnant evidence), ID (RR 0.62, 95% CI 0.50 to 0.76; 7 trials, 1088 women;
adolescents; low-certainty evidence). moderate-certainty evidence), and IDA (not estimated; GRADE:
not assessed), in women receiving daily oral iron compared with
Fortification (1 review) those not receiving daily oral iron supplementation. There was no
One review assessed MMN fortification (dose: not reported; evidence of a difference in any adverse side effect (RR 2.14, 95% CI
frequency: daily or weekly) for adolescents (Salam 2020). 0.94 to 4.86; 7 trials, 901 women; low-certainty evidence).
Prevention Treatment
MMN fortification versus no fortification Intravenous iron versus oral iron
Salam 2020 evaluated the effects of MMN for adolescents aged Sultan 2019 included 15 trials comprising 2182 women with a
10 to 19 years old. There is no evidence of a difference in Hb postdelivery Hb level of < 12 g/dL and assessed IV iron (dose/
concentration compared with no fortification (MD -0.10 g/L, 95% CI frequency: different dosages) compared with oral iron.
-0.88 to 0.68; 2 trials, 1102 participants; low-certainty evidence).
There was an increase in Hb at 1 week postpartum (MD 10.00 g/L,
Improving dietary diversity and quality 95% CI 5.00 to 15.00 (P < 0.0001); 11 trials, 1236 women; GRADE:
not assessed), at 2 weeks postpartum (MD 12.00 g/L, 95% CI 5.00 to
None of the included reviews assessed interventions aimed at 19.00 (P = 0.0007); 7 trials, 980 women; GRADE: not assessed), at 3
improving dietary diversity and quality for adolescent children weeks postpartum (MD 13.00 g/L, 95% CI 0.60 to 26.00 (P = 0.04);
aged 11 to 18 years. 2 trials, 346 women; GRADE: not assessed), at 6 weeks postpartum
(MD 9.00 g/L, 95% CI 4.00 to 13.00 (P = 0.0003); 4 trials, 385 women;
Non-pregnant women of reproductive age (aged 19 to 49 GRADE: not assessed), but there was no evidence of a difference at
years) (5 reviews) 4 weeks postpartum (MD 7.00 g/L, 95% CI -3.00 to 16.00 (P = 0.18),
Five systematic reviews assessed interventions to prevent or 4 trials, 583 women; GRADE: not assessed).
control anaemia in non-pregnant women of reproductive age (aged
19 to 49 years) (Abe 2016; Houston 2018; Lassi 2020; Low 2016; Four trials showed that IV iron increased skin flushing compared
Sultan 2019). GRADE assessments were provided in two out of five with oral iron (OR 6.95, 95% CI 1.56 to 31.03 (P = 0.01); 4 trials,
reviews. The effects of the interventions are summarised in Table 281 women; GRADE: not assessed). IV iron decreased constipation
24. (OR 0.08, 95% CI 0.03 to 0.21 (P < 0.00001); 8 trials, 1535 women;
GRADE: not assessed), and dyspepsia (OR 0.07, 95% CI 0.01 to 0.42
Supplementation (5 reviews) (P = 0.004); 3 trials, 304 women; GRADE: not assessed). However,
there was no evidence of a difference in other treatment-related
Five systematic reviews assessed the effects of supplementation side effects, including nausea, muscle cramps, alanine transferase
interventions in non-pregnant women of reproductive age (Abe rise, aspartate transaminase rise, headache, anaphylaxis, urticaria,
2016; Houston 2018; Lassi 2020; Low 2016; Sultan 2019). See Table rash, and infection between IV iron and oral iron.
24.
Prevention and/or treatment
Iron supplementation
Iron therapy (oral, IV, IM) versus control
Three reviews assessed iron supplementation for non-pregnant
women of reproductive age (Houston 2018; Low 2016; Sultan 2019). Eighteen RCTs comprising 1170 participants (age range = 17 to 55
See Table 24. years) who were iron deficient but non-anaemic were included
in the Houston 2018 systematic review. This review assessed the
Prevention effects of iron therapy (oral (dose: 16 mg to 200 mg; frequency:
Daily oral iron supplementation with or without co-intervention (folic
daily), IV (dose: 200 mg to 1000 mg; frequency: daily), IM (dose:
acid or vitamin C) versus no supplemental iron 100 mg; frequency: daily)) on fatigue and physical capacity in iron-
deficient non-anaemic (IDNA) adults (15 trials included women only
Sixty-seven trials comprising 8506 menstruating women (13 to with more than 60% within this age group). Iron therapy increased
45 years, 3 trials included adolescent girls only) were included Hb levels compared with control (MD 4.01 g/L, 95% CI 1.22 to 6.81;
in the systematic review by Low 2016. This review assessed the 12 trials, 298 women; GRADE: not assessed). Anaemia was less
effects of daily supplementation with iron (dose: 1 mg to 300 common in patients randomised to receive iron supplementation
mg of elemental iron; frequency: per day) on anaemia and iron (2 trials, 327 women). There was no clear difference between the
status (Hb, anaemia, IDA, ID) as well as on physical, psychological intervention group and the control group for the other outcomes:
and neurocognitive health. IDA was defined by the presence of gastrointestinal intolerance (3 trials, 262 women), nausea (4 trials,
anaemia plus iron deficiency, diagnosed with an indicator of iron 540 women), constipation (1 trial, 24 women), and diarrhoea
(Review)
Informed decisions.
(2 trials, 114 women). However, this systematic review reported Iron supplementation
increases in gastrointestinal intolerance and nausea in trials The effect of iron supplementation during pregnancy was assessed
using IM or IV iron administration, but not in trials using oral in 11 reviews (Daru 2016; Govindappagari 2019; Haider 2013; Imdad
administration. 2012; Peña-Rosas 2015a; Peña-Rosas 2015b; Qassim 2018; Qassim
Prevention 2019; Radhika 2019; Reveiz 2011; Shi 2015). See Table 25.
Iron folic acid supplementation versus placebo Prevention
Lassi 2020 included 10 trials comprising 8955 periconceptional Daily iron supplementation
women, and assessed the effects of iron folic acid supplementation Fourty-eight RCTs and cluster-RCTs randomising 17,793 women
(dose: different dosages; frequency: daily/weekly). were included in one review assessing prenatal iron use (dose: 10
Comparing iron folic acid supplementation with placebo showed mg to 240 mg (1 trial used a daily dose of 900 mg); frequency: daily)
a reduction in the incidence of anaemia (RR 0.66, 95% CI 0.53 in pregnant women of any gestational age (Haider 2013). IDA was
to 0.81; 6 trials, 3430 women; very low-certainty evidence). Also, defined as Hb less than 110 g/L and serum ferritin less than 12
there was a reduction in the incidence of anaemia with weekly μg/L, and ID was defined as serum ferritin less than 12 μg/L. Iron
supplementation (RR 0.70, 95% CI 0.55 to 0.88; 6 trials, 2661 women; interventions with or without folic acid increased Hb concentration
very low-certainty evidence) and daily supplementation (RR 0.49, in the third trimester or at delivery (WMD 4.59 g/L, 95% CI 3.72 to
95% CI 0.21 to 1.12; 2 trials, 1532 women; very low-certainty 5.46; 36 trials; GRADE: not assessed) and in the postpartum period
evidence). (WMD 6.79 g/L, 95%CI 0.22 to 13.36; 12 trials; GRADE: not assessed),
but not in the second trimester (WMD −0.23 g/L, 95% CI −12.18 to
Prevention 11.72; 8 trials; GRADE: not assessed). The intervention also reduced
anaemia in (RR 0.50, 95% CI 0.42 to 0.59; 20 trials; GRADE: not
Two RCTs comprising 52 breastfeeding women were included in the
assessed), IDA (RR 0.40, 95% CI 0.26 to 0.60; 6 trials; GRADE: not
systematic review by Abe 2016. This review assessed the effects
assessed), and ID in the third trimester or at delivery (RR 0.59, 95%
and safety of MMN supplementation (dose: 18 mg to 45 mg iron;
CI 0.44 to 0.79; 8 trials; GRADE: not assessed). Women receiving
frequency: daily) in breastfeeding mothers on maternal and infant
iron only compared with no iron or placebo showed increased Hb
outcomes, but no data were available for outcomes related to
concentrations in the third trimester or at delivery (WMD 4.50 g/
anaemia.
L, 95% CI 3.62 to 5.39; 31 trials; GRADE: not assessed) and in the
Fortification postpartum period (WMD 7.01 g/L, 95% CI 0.36 to 13.66; 8 trials;
GRADE: not assessed), as well as reduced anaemia (RR 0.56, 95%
None of the included reviews assessed fortification interventions CI 0.48 to 0.65; 17 trials; GRADE: not assessed), IDA (RR 0.37, 95%
for non-pregnant women of reproductive age. CI 0.23 to 0.60; 5 trials; GRADE: not assessed) and ID in the third
trimester or at delivery (RR 0.59, 95% CI 0.44 to 0.79; 8 trials; GRADE:
Improving dietary diversity and quality not assessed). Iron with folic acid increased Hb levels (WMD 10.41
None of the included reviews assessed interventions aimed at g/L, 95% CI 5.36 to 15.46; 9 trials; GRADE: not assessed) and reduced
improving dietary diversity and quality for non-pregnant women of anaemia (RR 0.44, 95% CI 0.37 to 0.53; 5 trials; GRADE: not assessed)
reproductive age. in the third trimester or at delivery compared with no iron and folic
acid or placebo.
Pregnant women of reproductive age (aged 15 to 49 years) (23
reviews) Another review, Imdad 2012, included 30 RCTs, cluster-RCTs and
quasi-RCTs to assess the impact of routine iron supplementation
Twenty-three systematic reviews assessed interventions to prevent (dose: 20 mg to 300 mg; frequency: daily) in pregnant women.
or control anaemia in pregnant women of reproductive age (Abu Women receiving iron supplementation had a reduced risk of
Hashim 2017; Bhutta 2012; Buppasiri 2015; Daru 2016; Das 2018; anaemia at term (RR 0.31, 95% CI 0.22 to 0.44; 18 trials, 8665
De-Regil 2015; Govindappagari 2019; Haider 2011; Haider 2013; women; moderate-certainty evidence) and IDA (defined as Hb less
Imdad 2012; Keats 2019; Lassi 2013; McCauley 2015; Peña-Rosas than 110 g/L) at term (RR 0.44, 95% CI 0.28 to 0.68; 7 trials; GRADE:
2015a; Peña-Rosas 2015b; Qassim 2018; Qassim 2019; Radhika not assessed) compared with women receiving no iron. There was
2019; Reveiz 2011; Rumbold 2015; Shi 2015; Suchdev 2015; Thorne- no evidence of a difference for severe anaemia at any time during
Lyman 2012). One additional review, focusing on school-aged the second and third trimester (RR 0.25, 95% CI 0.03 to 2.48; 13
children, also presented results for pregnant women, and is trials; GRADE: not assessed) or at term (RR 4.83, 95% CI 0.23 to 99.88;
included here as well (Aaron 2015). GRADE assessments were 11 trials; GRADE: not assessed).
provided in 12 out of 23 reviews. The results are summarised
in Table 25. Peña-Rosas 2015b conducted a comprehensive review assessing
the effects of daily oral iron supplementation (dose: 9 mg to 900
Supplementation (22 reviews) mg; frequency: daily) for pregnant women of any gestational age,
Twenty-two reviews assessed supplementation interventions in which included 61 RCTs, cluster-RCTs and quasi-RCTs, randomising
pregnant women (Abu Hashim 2017; Bhutta 2012; Buppasiri 2015; a total of 43,274 women. Maternal IDA at term was defined by
Daru 2016; Das 2018; De-Regil 2015; Govindappagari 2019; Haider trialists at 37 weeks’ gestation or more, and maternal ID at term
2011; Haider 2013; Imdad 2012; Keats 2019; Lassi 2013; McCauley was defined by trialists, based on any indicator of iron status at
2015; Peña-Rosas 2015a; Peña-Rosas 2015b; Qassim 2018; Qassim 37 weeks’ gestation or more. Any supplements containing iron
2019; Radhika 2019; Reveiz 2011; Rumbold 2015; Shi 2015; Thorne- compared with the same supplements without iron or no treatment
Lyman 2012). See Table 25. or placebo increased maternal Hb concentration at or near term
(Review)
Informed decisions.
(MD 8.88 g/L, 95% CI 6.96 to 10.80; 19 trials, 3704 women; GRADE: and minerals) increased maternal anaemia at or near term (RR 1.66,
not assessed) and within six weeks postpartum (MD 7.61 g/L, 95% 95% CI 1.09 to 2.53; 8 trials, 1385 women; GRADE: not assessed) and
CI 5.50 to 9.72; 7 trials, 956 women; GRADE: not assessed). The increased maternal ID at or near term (RR 2.38, 95% CI 1.30 to 4.36;
intervention reduced maternal anaemia (RR 0.30, 95% CI 0.19 to 3 trials, 587 women; GRADE: not assessed). There was no evidence
0.46; 14 trials, 2199 women; low-certainty evidence), IDA (RR 0.33, of a difference between the groups for maternal Hb at or near
95% CI 0.16 to 0.69; 6 trials, 1088 women; GRADE: not assessed), ID term (MD −2.57, 95% CI −5.18 to 0.04; 8 trials, 1306 women; GRADE:
(RR 0.43, 95% CI 0.27 to 0.66; 7 trials, 1256 women; low-certainty- not assessed), maternal anaemia at term (RR 1.22, 95% CI 0.84 to
evidence) at term (or near term), and severe anaemia postpartum 1.80; 4 trials, 676 women; very low-certainty evidence), moderate
(RR 0.04, 95% CI 0.01 to 0.28; 8 trials, 1339 women; GRADE: not anaemia at any time during the second and third trimester (RR 2.50,
assessed). There was no evidence of a difference between the 95% CI 0.84 to 7.48; 9 trials, 1291 women; GRADE: not assessed),
groups for the outcomes of moderate anaemia at postpartum (RR maternal IDA at term (RR 0.71, 95% CI 0.08 to 6.63; 1 trial, 156
0.55, 95% CI 0.12 to 2.51; 3 trials, 766 women; GRADE: not assessed), women; very low-certainty evidence) or near term (RR 2.06, 95% CI
maternal severe anaemia at any time during the second and third 0.65 to 6.61; 2 trials, 278 women; GRADE: not assessed) and severe
trimester (RR 0.22, 95% CI 0.01 to 3.20; 9 trials, 2125 women; very anaemia at postpartum (RR 0.43, 95% CI 0.04 to 4.64; 1 trial, 169
low-certainty evidence), maternal severe anaemia at or near term women; GRADE: not assessed). There were no events reported for
(RR 0.47, 95% CI 0.01 to 44.11; 8 trials, 1819 women; GRADE: not severe anaemia at any time during second and third trimesters
assessed). There was also no evidence of a difference between (6 trials, 1240 women), severe anaemia at or near term (6 trials,
the iron supplementation and control groups for side effects (RR 1050 women) and severe anaemia at term (3 trials, 475 women).
1.29, 95% CI 0.83 to 2.02; 11 trials, 2423 women; very low-certainty Women receiving intermittent iron supplementation experienced
evidence). While diarrhoea was reduced for women receiving iron fewer side effects (RR 0.56, 95% CI 0.37 to 0.84; 11 trials, 1777
supplementation compared with the same supplements without women; very low-certainty evidence) and there were no differences
iron or no treatment or placebo (RR 0.55, 95% CI 0.32 to 0.93; 3 trials, between the groups for diarrhoea (RR 0.80, 95% CI 0.32 to 2.00;
1088 women; GRADE: not assessed), there were no differences 5 trials, 613 women; GRADE: not assessed), constipation (RR 0.85,
between the groups for constipation (RR 0.95, 95% CI 0.62 to 1.43; 95% CI 0.45 to 1.59; 6 trials, 733 women; GRADE: not assessed) or
4 trials, 1495 women; GRADE: not assessed) and vomiting (RR 0.88, vomiting (RR 1.30, 95% CI 0.79 to 2.15; 6 trials, 954 women; GRADE:
95% CI 0.59 to 1.30; 4 trials, 1392 women; GRADE: not assessed). In a not assessed).
second comparison, any supplements containing iron and folic acid
versus the same supplements without iron nor folic acid (no iron Treatment
nor folic acid or placebo) showed increased maternal Hb levels at or Oral, IV or IM iron interventions
near term (MD 16.13 g/L, 95% CI 12.74 to 19.52; 3 trials, 140 women;
GRADE: not assessed) and within six weeks postpartum (MD 10.07 Govindappagari 2019 included 11 RCTs with 1190 pregnant women
g/L, 95% CI 7.33 to 12.81; 2 trials, 459 women; GRADE: not assessed). with IDA to assess the impact of IV iron (dose: a maximum daily
Any supplements containing iron and folic acid also resulted in a dose of 200 mg; frequency: infused in split doses every other day).
reduction of maternal anaemia at term (or near term) (RR 0.34, 95% Women receiving IV iron were more likely to reach their Hb target
CI 0.21 to 0.54; 3 trials, 346 women; moderate-certainty evidence), (OR 2.66, 95% CI 1.71 to 4.15; 7 trials; GRADE: not assessed), showed
moderate anaemia at postpartum (RR 0.33, 95% CI 0.17 to 0.65; 3 increased Hb levels after 4 weeks of treatment (WMD 0.84, 95% CI
trials, 491 women; GRADE: not assessed), maternal ID at term (or 0.59 to 1.09; 9 trials; GRADE: not assessed), and experienced fewer
near term) (RR 0.24, 95% CI 0.06 to 0.99; 1 trial, 131 women; low- adverse events compared with those receiving oral iron (OR 0.35,
certainty evidence), maternal severe anaemia at any time during 95% CI 0.18 to 0.67; 11 trials; GRADE: not assessed).
second and third trimester (RR 0.12, 95% CI 0.02 to 0.63; 4 trials, Qassim 2018 included 21 RCTs involving administration of IV
506 women; very low-certainty evidence) and severe anaemia at iron (ferric carboxymaltose, iron polymaltose or iron sucrose)
postpartum (RR 0.05, 95% CI 0.00 to 0.76; 3 trials, 491 women; to manage antenatal IDA (dose: different dosages; frequency:
GRADE: not assessed). There were no differences between the daily). All IV preparations showed improvements in haematological
intervention and control groups for maternal IDA at term (or near parameters, with an overall median increase of 21.8 g/L at 3 to
term) (RR 0.43, 95% CI 0.17 to 1.09; 1 trial, 131 women; GRADE: not 4 weeks and 30.1 g/L by delivery. Qassim 2019 also assessed the
assessed) and maternal severe anaemia at or near term (RR 0.14, effects of IV and oral iron therapy for IDA in pregnant women with 15
95% CI 0.01 to 2.63; 3 trials, 191 women; GRADE: not assessed). trials (dose: different dosages; frequency: daily). Women receiving
However, the intervention increased the risk of side effects (RR IV iron therapy showed increases in Hb concentration (MD 7.40, 95%
44.32, 95% CI 2.77 to 709.09; 1 trial, 456 women; moderate-certainty CI 3.90 to 10.90; 9 trials, 1009 women; low-certainty evidence), but
evidence). no influence in Hb concentration of neonates at delivery (MD -1.00,
Intermittent iron supplementation 95% CI -4.70 to 2.80; 6 trials, 849 neonates; low-certainty evidence)
compared to oral iron supplementation.
Peña-Rosas 2015a included 21 RCTs, cluster-RCTs and quasi-RCTs
of 5490 pregnant women of any gestational age to examine Radhika 2019 included 18 RCTs with 1633 antenatal women with
intermittent iron supplementation with or without other vitamins IDA to assess the effects of IV iron sucrose compared with oral
and minerals (dose: 80 mg to 300 mg elemental iron; frequency: iron therapy (dose: not reported; frequency: daily). Cumulative
weekly). Maternal IDA at term was defined as Hb less than 110 analysis showed increases in Hb concentration for women receiving
g/L and at least one additional laboratory indicator at 37 weeks’ IV iron sucrose compared to oral iron supplementation at all
gestation or more, and maternal ID at term was defined by trialists, time points (MD 0.78 g/L 95% CI 0.57 to 1.00; 11 trials, 3460
based on any indicator of iron status at 37 weeks’ gestation or more. women; high-certainty evidence) and at the end of six weeks'
Any intermittent iron regimen (with or without other vitamins and evaluation (MD 0.66 g/L, 95% CI 0.29 to 1.04; 9 trials, 1147 women;
minerals) compared with daily regimen (with the same vitamins high-certainty evidence). For postpartum women, the cumulative
(Review)
Informed decisions.
analysis showed increases in Hb concentration for those receiving decreased mean Hb levels at 36 weeks' gestation (MD −2.60 g/L,
IV iron sucrose compared to oral iron supplementation from the 95% CI −4.80 to −0.40; 1 trial, 150 women; GRADE: not assessed),
first week to six weeks of observation (MD 0.83 g/L, 95% CI 0.42 to but had no effect on diarrhoea or constipation, compared with oral
1.25; 8 trials, 1370 women; moderate-certainty evidence), but no iron plus folic acid. One trial assessed the effect of daily compared
statistical difference at six weeks. to twice a week oral iron and found an increase in Hb levels at
four weeks (MD 5.40 g/L, 95% CI 1.40 to 9.40; 1 trial, 160 women;
In Shi 2015, six RCTs and a total of 576 pregnant women with GRADE: not assessed), eight weeks (MD 11.70 g/L, 95% CI 6.70 to
diagnosed IDA were included to assess the efficacy and safety of 16.70; 1 trial, 129 women; GRADE: not assessed) and 12 weeks (MD
IV iron sucrose (dose: weight × (11 g/dL or 12 g/dL – actual Hb) 12.70 g/L, 95% CI 6.80 to 18.60; 1 trial, 105 women; GRADE: not
× 0.24 + 500 mg; frequency: every other day) compared with oral assessed) but not at 16 weeks. Oral iron daily versus oral iron once
iron supplementation (dose: 100 mg to 300 mg elemental iron; a week increased Hb levels (MD 7.00 g/L, 95% CI 3.60 to 10.40;
frequency: daily). Women receiving IV iron showed increased Hb 1 trial, 97 women; GRADE: not assessed) as did oral iron twice
levels at the end of treatment (MD 8.50, 95% CI 3.10 to 13.90; 6 a week versus oral iron once a week (MD 4.00 g/L, 95% CI 0.30
trials, 576 women; GRADE: not assessed) and fewer adverse events to 7.70; 1 trial, 101 women; GRADE: not assessed). There was no
at the of treatment (RR 0.50, 95% CI 0.34 to 0.73; 4 trials, 439 women; improvement in Hb levels at delivery for IV iron sucrose 500 mg
GRADE: not assessed) compared with oral iron supplementation. versus IV iron sucrose 200 mg. IV iron sucrose 500 mg increased
Hb levels at birth (MD 16.00 g/L, 95% CI 8.70 to 23.30; 1 trial, 40
Another review included 23 RCTs, randomising 3198 pregnant
women; GRADE: not assessed) compared with IM iron sorbitol, as
women of any gestational age with diagnosed anaemia attributed
did IV iron sucrose 200 mg (MD 11.00 g/L, 95% CI 4.90 to 17.10; 1 trial,
to ID, to examine the effects of different treatments for anaemia
45 women; GRADE: not assessed) compared with IM iron sorbitol.
during pregnancy (dose/frequency: daily or weekly oral iron 20 mg
Oral iron polymaltose complex (100 mg) compared with ferrous
to 300 mg; IM iron dose depending on body weight and Hb deficit
sulphate (120 mg) improved constipation at eight weeks (RR 0.30,
and injected on alternating day; IV maximum total dose of iron
95% CI 0.14 to 0.64; 1 trial, 100 women; GRADE: not assessed), but
ranged from 200 mg to 500 mg injected every other day or twice
not Hb levels at eight weeks or diarrhoea. Oral bovine lactoferrin
weekly) (Reveiz 2011). Women receiving oral iron supplementation
compared with ferrous sulphate decreased mean Hb levels at
compared with placebo showed increased Hb levels (MD 13.40 g/
one month (MD −3.00, 95% CI −5.20 to −0.80; 1 trial, 97 women;
L, 95% CI 2.70 to 24.20; 2 trials, 215 women; GRADE: not assessed)
GRADE: not assessed). At eight weeks, there was no difference in
and reduced anaemia during the second trimester (RR 0.38, 95%
Hb levels, the rate of anaemia, the rate of moderate anaemia or
CI 0.26 to 0.55; 1 trial, 125 women; GRADE: not assessed). Only one
vomiting for women receiving ferrous sulphate (elementary iron)
trial with 51 women assessed side effects, nausea and vomiting
20 mg compared with 40 mg of iron (1 trial). However, when
or constipation for this comparison, and found no differences
compared to 80 mg of ferrous sulphate, the intervention of 20 mg
between the groups. Oral iron plus vitamin A versus placebo also
ferrous sulphate resulted in decreased Hb levels at eight weeks (MD
resulted in an increase in Hb levels (MD 13.00 g/L, 95% CI 11.10 to
−8.00 g/L, 95% CI −12.70 to −3.30; 1 trial, 110 women; GRADE: not
14.90; 1 trial, 125 women; GRADE: not assessed) and a reduction
assessed) and reduced vomiting (RR 0.53, 95% CI 0.30 to 0.93; 1
in anaemia during the second trimester (RR 0.04, 95% CI 0.01 to
trial, 119 women; GRADE: not assessed) but no difference in the rate
0.15; 1 trial, 125 women; GRADE: not assessed). There were no
of anaemia at eight weeks and the rate of moderate anaemia at
differences for side effects, nausea and vomiting or constipation
eight weeks. The intervention of 40 mg ferrous sulphate resulted
for the comparisons controlled-release oral iron versus regular oral
in a reduction of Hb levels at eight weeks (MD −5.00 g/L, 95% CI
iron (1 trial, 49 women), IV iron versus placebo (1 trial, 54 women)
−9.30 to −0.70; 1 trial, 112 women; GRADE: not assessed) but no
and IV iron versus controlled-release oral iron (1 trial, 52 women).
difference in the rate of anaemia at eight weeks and the rate of
There were also no differences for nausea or vomiting for the
moderate anaemia at eight weeks and vomiting at eight weeks
comparisons IM iron sorbitol-citric acid versus IM dextran (1 trial, 48
when compared with 80 mg ferrous sulphate. The combination of
women), IM iron dextran versus IV iron dextran (1 trial, 49 women)
IV iron and oral iron increased the mean pre-delivery maternal Hb
and IM iron sorbitol citric acid versus IV iron dextran (1 trial, 51
levels (MD 4.80 g/L, 95% CI 2.10 to 7.50; 1 trial, 183 women; GRADE:
women). IV iron versus regular oral iron increased maternal Hb
not assessed) and mean maternal Hb levels after delivery (MD 3.90
levels at birth (MD 7.50 g/L, 95% CI 3.40 to 11.60; 1 trial, 90 women;
g/L 95% CI 0.20 to 7.60; 1 trial, 112 women; GRADE: not assessed)
GRADE: not assessed) and mean maternal Hb levels at four weeks
compared with oral iron alone.
(MD 4.40 g/L, 95% CI 0.50 to 8.20; 3 trials, 167 women; GRADE: not
assessed), and reduced nausea or vomiting or epigastric discomfort Prevention and/or treatment
(RR 0.33, 95% CI 0.15 to 0.74; 3 trials, 244 women; GRADE: not
Oral, IV or IM iron interventions
assessed), constipation (RR 0.11, 95% CI 0.02 to 0.71; 2 trials, 151
women; GRADE: not assessed) and diarrhoea (RR 0.16, 95% CI 0.03 Daru 2016 included 23 RCTs and a total of 3525 pregnant women
to 0.86; 3 trials, 237 women; GRADE: not assessed), but not side at any gestation with non-anaemic ID (NAID) or IDA and assessed
effects (RR 0.38, 95% CI 0.11 to 1.31; 1 trial, 51 women; GRADE: the effects of iron interventions (oral, including fortified water, IV or
not assessed). IM iron sorbitol-citric acid versus oral iron increased IM) on iron stores and oxygen carrying capacity in pregnancy (dose/
mean maternal Hb concentration at birth (MD 5.40 g/L, 95% CI 3.00 frequency: for pregnant women with ID anaemia using weekly 200
to 7.80; 1 trial, 200 women; GRADE: not assessed) and the relative mg to 400 mg IV iron or 120 mg oral iron and 30 mg to 80 mg of
risk of being not anaemic at term (RR 1.23, 95% CI 1.01 to 1.48; oral iron for women with NAID on a weekly or daily basis). In three
1 trial, 200 women; GRADE: not assessed). IM iron dextran led to out of six trials, higher Hb levels were observed in pregnant women
an increase in not being anaemic at six weeks compared with oral with IDA receiving IV iron compared with oral iron supplementation.
iron with vitamin C and folic acid (RR 11.0, 95% CI 1.51 to 79.96; 1 One trial compared IV versus IM iron supplementation in pregnant
trial, 60 women; GRADE: not assessed). IM iron sorbitol citric acid women with IDA and observed higher Hb levels in the IV group.
(Review)
Informed decisions.
Daily oral iron resulted in higher Hb levels compared with weekly Prevention
oral iron supplementation in pregnant women with IDA in one Folate supplementation versus no intervention, placebo, or other
out of three trials. Different doses of oral iron supplementation in micronutrients without folate
pregnant women with IDA were compared in two trials and one
trial found an increase in Hb concentration in the higher dose De-Regil 2015 included five RCTs with a total of 7391 pregnant
arm. IM versus oral iron supplementation (1 trial) and alternative women of less than 12 weeks' gestation at the time of the
oral preparations versus a commonly used preparation in pregnant intervention. The review examined whether or not preconceptional
women with IDA showed no evidence of a difference between folate supplementation (dose: 0.4 mg to 4.0 mg folic acid;
the groups. Oral iron supplementation versus placebo in pregnant frequency: daily) reduces the risk of adverse pregnancy outcomes.
women with IDA or NAID was assessed in six trials and two trials However, none of the included trials reported on maternal anaemia
found increased Hb levels in the supplementation group. at or near term.
Vitamin A supplementation Thrity-one RCTs, cluster-RCTs and quasi-RCTs randomising 17,771

pregnant women of any age and parity were included in the Lassi
Two systematic reviews assessed vitamin A supplementation 2013 review, which assessed the effectiveness of oral folic acid
during pregnancy (McCauley 2015; Thorne-Lyman 2012). supplementation (dose: 10 μg to 400 μg folic acid; frequency: daily)
Prevention
alone or with other micronutrients. There was no evidence of a
difference between folic acid supplementation versus no folic acid
Vitamin A alone or with other micronutrients versus placebo or no supplementation during pregnancy for the outcomes of mean pre-
treatment or micronutrient supplements without vitamin A delivery Hb concentration (MD −0.03 g/L, 95% CI −0.25 to 0.19;
One review included 19 trials with over 310,000 pregnant women 12 trials, 1806 women; GRADE: not assessed) and pre-delivery
of any gestational age to assess the effects of vitamin A anaemia (RR 0.62, 95% CI 0.35 to 1.10; 8 trials, 4149 women; GRADE:
supplementation (dose: mainly as capsules of 5750 IU to 444,000 not assessed).
IU of vitamin A; frequency: daily or weekly) during pregnancy
MMN supplementation
(McCauley 2015). Vitamin A supplementation alone reduced
maternal anaemia (RR 0.64, 95% CI 0.43 to 0.94; 3 trials, 3818 Three reviews assessed MMN supplementation with iron and folic
women; moderate-certainty evidence) compared with placebo or acid during pregnancy (Bhutta 2012; Haider 2011; Keats 2019).
no treatment. However, vitamin A supplementation with other
micronutrient versus micronutrient supplements without vitamin Prevention
A showed no clear effect on maternal anaemia (RR 0.86, 95% CI 0.68 MMN with iron and folic acid versus iron and folic acid alone
to 1.09; 3 trials, 706 women; low-certainty evidence).
Seven RCTs and cluster-RCTs of 18,595 healthy pregnant women
Prevention and/or treatment of any gestation were included in the Bhutta 2012 review, which
assessed MMN supplementation during pregnancy to prevent
Vitamin A versus placebo or other MNs
maternal anaemia (dose: United Nations International Multiple
Thorne-Lyman 2012 included 17 RCTs and cluster-RCTs and Micronutrient Antenatal Preparation (UNIMMAP) formulation;
investigated the effect of vitamin A supplementation during frequency: at least 6 days/week). MMN versus iron and folic
pregnancy (dose: 3333 IU to 10,000 IU; frequency: daily or weekly). acid supplementation showed no improvement in maternal Hb
Vitamin A supplementation during pregnancy resulted in an concentration (SMD −0.01 g/L, 95% CI −0.08 to 0.06; 4 trials; low-
increase in maternal Hb concentration (MD 3.50 g/L, 95% CI 2.40 certainty evidence) or reduced the risk of maternal anaemia in the
to 4.50; 6 trials, 1034 women; moderate-certainty evidence) and a third trimester (RR 1.03, 95% CI 0.94 to 1.12; 7 trials; moderate-
reduction in maternal anaemia (RR 0.81, 95% CI 0.69 to 0.94; 6 trials, certainty evidence).
1587 women; high-certainty evidence), but not severe anaemia
(RR 0.93, 95% CI 0.59 to 1.45; 2 trials, 961 women; low-certainty Haider 2011 included 14 RCTs and cluster-RCTs and evaluated
evidence) compared with placebo or multivitamins. the impact of MMN supplements for pregnant women of any
gestation (dose: UNIMMAP formulation; frequency: daily). MMN
Prevention supplementation, including iron and folic acid versus iron or folate
One review included 29 RCTs and quasi-RCTs with a total of 24,300 supplementation alone showed no effect on maternal anaemia in
pregnant women of any gestational age to assess the effects of the third trimester (RR 1.03, 95% CI 0.87 to 1.22; 4 trials, high-
vitamin C supplementation during pregnancy (dose: commonly certainty evidence).
used 1000 mg/day (250 mg to 2000 mg); frequency: daily) (Rumbold In Keats 2019, 21 RCTs and cluster-RCTs randomising 142,496
2015). None of the included trials reported on the outcomes pregnant women of any gestational age were included to assess
of maternal Hb concentration and maternal anaemia. Vitamin C the benefits of oral MMN supplementation (dose: different dosages;
supplementation, alone or in combination with other supplements, frequency: daily). Consistent with the two other reviews, no
did not increase the outcome of "any side effect" (RR 1.16, 95% difference was observed for MMN with iron and folic acid compared
CI 0.39 to 3.41; 1 trial 707 women; GRADE: not assessed), but did with iron with or without folic acid supplementation on maternal
increase the outcome of "abdominal pain" (RR 1.66, 95% CI 1.16 to anaemia (RR 1.04, 95% CI 0.94 to 1.15; 9 trials; GRADE: not
2.37; 1 trial, 1877 women; GRADE: not assessed). assessed). However, MMN with iron and folic acid versus placebo
Folic acid supplementation showed a reduction of maternal anaemia (RR 0.66, 95% CI 0.51 to
0.85; 1 trial; GRADE: not assessed).
Two reviews evaluated the effect of folic acid supplementation
during pregnancy (De-Regil 2015; Lassi 2013).
(Review)
Informed decisions.
Prevention MNP for point-of-use fortification of foods versus iron and folic acid
supplementation or same MMN as supplements
Twenty-five RCTs randomising 18,578 pregnant women were
included in the Buppasiri 2015 systematic review. This review Suchdev 2015 included two cluster-RCTs, randomising 1172
assessed the effect of calcium supplementation (dose: 300 mg to pregnant women of any age and gestation, and assessed the
2000 mg; frequency: daily) other than for preventing or treating effects of prenatal home fortification of foods with MNP on
hypertension and found no evidence of a difference in maternal maternal Hb concentration and anaemia (dose: different dosages;
anaemia for women receiving calcium supplementation during frequency: daily or weekly). Women receiving MNP for point-of-
pregnancy compared with placebo or no treatment (RR 1.04, 95% use fortification of foods showed reduced Hb levels at 32 weeks'
CI 0.90 to 1.22; 1 trial, 1098 women; GRADE: not assessed). gestation (MD −2.50 g/L, 95% CI −4.85 to −0.15; 1 trial, 405 women;
GRADE: not assessed) and increased risk of any anaemia at 32
Prevention weeks' gestation (RR 1.25, 95% CI 1.00 to 1.57; 1 trial, 405 women;
Das 2018 included 3 RCTs and 1 cluster-RCT with 8018 pregnant GRADE: not assessed) compared with women receiving iron and
women (dose: 118 kcal/day or 372 kcal/day; frequency: daily). One folic acid supplements. There were no clear differences in maternal
study showed an increase in the prevalence of maternal anaemia Hb levels at term or near term (MD 1.00 g/L, 95% CI −1.77 to 3.77; 1
in the LNS group compared to iron and folic acid (RR 2.35, 95% CI trial, 470 women; GRADE: not assessed) and maternal anaemia at
1.67 to 3.30; 1 trial, 536 women; moderate-certainty evidence), but term or near term (RR 0.92, 95% CI 0.53 to 1.59; 1 trial, 470 women;
no difference in adverse effects (hospitalisation episode) between very low-certainty evidence) for women receiving MNP for point-of-
the groups (RR 1.34, 95% CI 0.93 to 1.94; 1 trial, 881 women; use fortification of foods compared with women receiving the same
GRADE: not assessed). Compared to MMN, the same study showed MMN in supplements.
an increase in the prevalence of maternal anaemia in the LNS group
(RR 1.40, 95% CI 1.07 to 1.82; 1 trial, 557 women; moderate-certainty
evidence), but no difference in adverse effects (hospitalisation None of the included reviews assessed interventions to improve
episode) between the groups (RR 1.18, 95% CI 0.83 to 1.68; 1 trial, dietary diversity and quality during pregnancy.
879 women; GRADE: not assessed).
Older adult women (aged 50 to 65 years and above)
Treatment
None of the included reviews focused only on older adult women
One review including four RCTs and 600 pregnant women with IDA aged 50 to 65 years and above.
assessed the efficacy of oral bovine lactoferrin (dose/frequency:
100 mg twice a day or 250 mg once a day) (Abu Hashim Adult men (aged 19 to 65 years and above)
2017). Oral bovine lactoferrin supplementation, compared with
None of the included reviews focused only on adult men aged 19 to
oral ferrous iron preparations, increased Hb levels at four weeks
65 years and above.
(MD 7.70 g/L, 95% CI 0.40 to 15.50; 4 trials, 600 women; low-
certainty evidence) and reduced the gastrointestinal side effects of Mixed population (all ages) (22 reviews)
'epigastric discomfort' (OR 0.11, 95% CI 0.05 to 0.22; 2 trials, 328
women; moderate-certainty evidence), 'vomiting' (OR 0.32, 95% CI Twenty-two systematic reviews assessed interventions to prevent
0.15 to 0.67; 2 trials, 328 women; moderate-certainty evidence), or control anaemia in mixed populations (Arabi 2020; Basutkar
'constipation' (OR 0.22, 95% CI 0.12 to 0.40; 2 trials, 328 women; 2019; Casgrain 2012; Das 2019b; Field 2020; Finkelstein 2019;
moderate-certainty evidence), 'abdominal colicky pain' (OR 0.21, Garcia-Casal 2018; Geerligs 2003; Gera 2007a; Gera 2009; Gera 2012;
95% CI 0.12 to 0.39; 1 trial, 228 women; moderate-certainty Hess 2016; Huo 2015; Peña-Rosas 2019; Ramírez-Luzuriaga 2018;
evidence), 'dark stool' (OR 0.01, 95% CI 0.00 to 0.22; 1 trial, 228 Sadighi 2019; Silva Neto 2019; Smelt 2018;Tablante 2019; Tay 2015;
women; moderate-certainty evidence), but not 'diarrhoea' (OR 0.0, Tolkien 2015; Yadav 2019). GRADE assessments were provided in 6
95% CI 0.0 to 0.0; 1 trial, 228 women; GRADE: not assessed). out of 22 reviews. The results are summarised in Table 26.
Fortification (2 reviews) Supplementation (9 reviews)
Two reviews assessed fortification interventions in pregnant Nine systematic reviews assessed supplementation interventions
women (Aaron 2015; Suchdev 2015). in mixed populations (Arabi 2020; Basutkar 2019; Casgrain 2012;
Gera 2007a; Gera 2009; Silva Neto 2019; Smelt 2018; Tay 2015;
Prevention Tolkien 2015). Five systematic reviews focused on prevention
Non-dairy MMN-fortified beverages versus iso-caloric non-fortified
(Casgrain 2012; Gera 2007a; Gera 2009; Smelt 2018; Tay 2015), one
beverage on treatment (Basutkar 2019), and three reviews on prevention
and/or treatment (Arabi 2020; Silva Neto 2019; Tolkien 2015).
Aaron 2015 included 10 trials with a total of 4645 participants See Table 26.
and evaluated the impact of MMN-fortified beverages on Hb levels
in school-aged children and women of reproductive age (dose: Iron supplementation
not reported; frequency: daily). There was a clear improvement in
Iron supplementation in mixed population was assessed in six
Hb levels for pregnant women receiving non-dairy MMN-fortified
reviews (Casgrain 2012; Gera 2007a; Gera 2009; Silva Neto 2019; Tay
beverages compared with iso-caloric non-fortified beverages (1
2015; Tolkien 2015).
trial, 439 women).
(Review)
Informed decisions.
Prevention RCTs evaluated Hb concentrations for adolescents and adults

Iron supplementation versus placebo or control and found no difference between the dietary plan group and
the iron supplementation group (MD 0.04 g/L, 95% CI −2.50 to
Forty-one RCTs randomising 3577 healthy adults aged 18 years 2.58; 165 participants; GRADE: not assessed). In one RCT, there
and over were included in the systematic review by Casgrain 2012. was an increase in Hb levels for pregnant women receiving iron
The review assessed the effects of iron supplementation versus supplementation compared to those receiving dietary intervention
placebo or control on Hb in healthy adults. There was an increase in (113.30 (± 8.80) g/L versus 112.40 (± 8.40) g/L; GRADE: not assessed).
Hb concentration for participants receiving iron supplementation
compared with those receiving placebo or control (MD 5.10 g/ Oral iron supplementation versus placebo or IV iron
L, 95% CI 3.70 to 6.50, 49 arms, 3577 participants, GRADE: not Forty-three RCTs and cross-over RCTs randomising 6831 adults
assessed). (including pregnant women) were included in the Tolkien
Another review, Gera 2007a, included 55 RCTs and cluster-RCTs 2015 review. This review evaluated the effect of ferrous
randomising over 12,198 children from birth to 19 years of age and sulphate supplementation on Hb, gastrointestinal side effects,
compared oral or parenteral iron supplementation (dose: 5 mg/ and individual side effects in adults. Oral iron supplementation
day to 120 mg/day or 1 mg/kg/day to 4 mg/kg/day) with placebo. increased the risk of gastrointestinal side effects (OR 2.32, 95% CI
This review evaluated the effect of oral iron supplementation on 1.74 to 3.08; 20 trials, 3168 participants) compared with placebo.
Hb in children and found an increase in Hb concentration for the Adults (including pregnant women) receiving IV iron showed higher
intervention group (WMD 7.40 g/L, 95% CI 6.10 to 8.70; 55 trials, Hb levels compared with those receiving oral iron supplementation
12,198 children; GRADE: not assessed). (20 trials). The risk of gastrointestinal side effects increased (OR
3.05, 95% CI 2.07 to 4.48; 23 trials) for adults receiving oral iron
In Tay 2015, three RCTs comprising 440 anaemic elderly people supplementation compared with those receiving IV iron. Adults
over 64 years of age were included in this systematic review. This (including pregnant women) receiving oral iron supplementation
review assessed the effectiveness of oral iron supplementation experienced higher incidences of constipation (12%, 95% CI 10%
on Hb and adverse effects in elderly people with IDA. The review to 15%; 27 trials), nausea (11%, 95% CI 8% to 14%; 30 trials), and
found higher levels of Hb (MD 3.50 g/L, 95 % CI 1.20 to 5.90; 3 diarrhoea (8%, 95% CI 6% to 11%; 25 trials), compared to those
trials, 438 elderly people; GRADE: not assessed) for elderly people receiving IV iron. An increase in the incidence of gastrointestinal
taking oral iron supplementation but no differences were observed side effects (OR 9.44, 95% CI 2.23 to 33.93; 5 trials, 561 pregnant
in adverse effects between the oral iron supplementation and no women) was observed for pregnant women receiving oral iron
supplementation or placebo groups. compared with IV iron.
Iron with MMN versus placebo, no treatment, or iron supplementation Prevention
Thirty RCTs were included in the systematic review by Gera 2009, Vitamin B12 or folic acid supplementation versus placebo
which examined the effects of multiple (2 or more) MNs with iron Seven RCTs randomising 1306 participants over 60 years of age
supplementation (dose: 5 mg to 60 mg; frequency: per day) versus were included in the Smelt 2018 review. The review examined
placebo, no treatment or iron supplementation alone in children the effect of vitamin B12 and folic acid supplementation on
from birth to 18 years of age. Hb levels increased for children
haematological parameters in an elderly population. There was no
receiving iron with MMN compared with placebo or no treatment
difference in Hb concentration (MD 0.00 g/L, 95% CI −0.19 to 0.18; 4
(WMD 6.50 g/L, 95% CI 5.00 to 8.00; 23 trials, 4981 participants;
trials, 343 participants) between the vitamin B12 supplementation
GRADE: not assessed). Hb slightly increased for children receiving
iron with MMN compared with iron supplementation alone (WMD group and placebo group. Similarly, there was no difference in Hb
1.40 g/L, 95% CI 0.00 to 2.80; 13 trials, 1483 participants; GRADE: not concentration (MD −0.09 g/L, 95% CI −0.19 to 0.01; 3 trials, 929
assessed). participants) between elderly participants allocated to receive folic
acid supplementation or placebo.
Prevention and/or treatment
Vitamin D supplementation
Dietary intervention and dietary plan or fortified foods versus iron
supplementation Vitamin D supplementation in mixed population was assessed in
two reviews (Arabi 2020; Basutkar 2019).
Twelve RCTS including 730 children, 164 adolescent or adults
and 85 pregnant women, irrespective of age, sex or race, were Treatment
included in the systematic review by Silva Neto 2019. This
Another review, Basutkar 2019, included 4 RCTs randomising
review compared the effects of a dietary intervention versus iron
over 429 patients with IDA, evaluated the efficacy of vitamin D
supplementation on Hb and other serum biochemical parameters
supplementation with placebo on Hb concentration and ferritin
related to iron nutritional status, in a standard treatment period
concentration. This review found no difference in Hb concentration
(defined as 12 weeks or more follow-up). Hb concentration
(MD -0.05, 95% CI -0.39 to 0.28; 4 trials, 407 participants; high-
increased for children with anaemia or IDA (MD 3.19 g/L, 95%
certainty evidence) and ferritin concentration (MD 1.70, 95% CI
CI 1.31 to 5.07; 425 children; GRADE: not assessed) who received
-9.12 to 12.53; 3 trials, 396 participants; high-certainty evidence)
supplementation but decreased for non-anaemic children (MD
between the vitamin D supplementation group and placebo group.
−6.58 g/L; 95% CI −11.52 to −1.64; 3 trials, 305 children, GRADE:
not assessed) who received dietary interventions. In three RCTs, Prevention and/or treatment
the prevalence of anaemia was lower after iron supplementation
compared with fortification (supplementation versus fortification: Fourteen RCTs were included in the systematic review by Arabi
4.3% versus 9.7%, 42.5% versus 54.9%, 6.6% versus 9.7%). Five 2020, which examined the effects of vitamin D supplementation on
(Review)
Informed decisions.
haemoglobin concentration in participants aged 17.5 to 68 years. Iron-biofortified staple crops versus conventional crops
There was no difference in Hb concentration (SMD 0.13, 95% CI Three RCTs comprising 633 adolescents and adults (including
-0.16 to 0.42; 1 RCT, 205 healthy adults; SMD 0.02, 95% CI -0.20 to pregnant or lactating women) were included in the Finkelstein
0.24; 2 RCTs, 466 anaemic patients) and ferritin concentration (SMD 2019 systematic review. This review assessed the effects of iron
-0.17, 95% CI -0.72 to 0.39; 3 RCTs, 303 healthy adults; SMD -0.18, biofortified staple crops versus conventional crops on improving
95% CI -0.36 to 0.01; 2 RCTs, 466 anaemic patients) for participants iron status and functional outcomes. ID was defined as serum
receiving vitamin D supplementation compared with the control ferritin < 15.0 μg/L. There was no difference in the risk of anaemia
group. (RR 0.83, 95% CI 0.58 to 1.19; 3 trials, 597 participants) and
Fortification (12 reviews) ID (RR 0.86, 95% CI 0.61 to 1.23; 3 trials, 603 participants) for
participants receiving iron-biofortified staple crops compared with
Twelve systematic reviews assessed fortification interventions in conventional crops.
mixed populations (Das 2019b; Field 2020; Finkelstein 2019; Garcia-
Casal 2018; Gera 2012; Hess 2016; Huo 2015; Peña-Rosas 2019; Maize flour or maize flour products fortified with iron plus other
Ramírez-Luzuriaga 2018; Sadighi 2019; Tablante 2019; Yadav 2019). vitamins and minerals versus unfortified maize flours or maize flour
products
One review includes is prevention and treatment (Peña-Rosas
2019), and the others are all prevention reviews (Das 2019b; Field Three RCTs and cluster-RCTs including 2610 participants and two
2020; Finkelstein 2019; Garcia-Casal 2018; Gera 2012; Hess 2016; uncontrolled before-after trials involving 849 participants were
Huo 2015; Ramírez-Luzuriaga 2018; Sadighi 2019; Tablante 2019; included in the Garcia-Casal 2018 review, which assessed the
Yadav 2019). See Table 26. effects of iron fortification of maize flour, corn meal and fortified
maize flour products for anaemia and iron status in the general
Prevention
population. Results from the RCTs showed no effect of maize flour
Ten reviews assessed iron-fortified foods in mixed populations or maize flour products fortified with iron plus other vitamins and
(Field 2020; Finkelstein 2019; Garcia-Casal 2018; Gera 2012; Huo minerals versus unfortified maize flours or maize flour products
2015; Peña-Rosas 2019; Ramírez-Luzuriaga 2018; Sadighi 2019; on Hb concentration (MD 1.25 g/L, 95% CI −2.36 to 4.86; 3 trials,
Tablante 2019; Yadav 2019). 1144 participants; very low-certainty evidence), anaemia (RR 0.90,
95% CI 0.58 to 1.40; 2 trials, 1027 participants; very low-certainty
Wheat flour fortified with iron alone or in combination with other evidence), IDA (RR 1.04, 95% CI 0.58, 1.88; 1 trial, 515 participants),
micronutrients versus unfortified wheat flour or fortified with the or ID (RR 0.75, 95% CI 0.49 to 1.15; 2 trials, 1102 participants; very
same micronutrients but not iron
low-certainty evidence). Adverse events were not reported in any of
Nine RCTs randomising 3166 participants over two years of the included trials.
age were included in the systematic review by Field 2020,
Fortification with iron versus control
which examined the effect of wheat flour fortified with iron
alone versus unfortified wheat flour, wheat flour fortified with Sixty RCTs, cluster-RCTs, and quasi-RCTs comprising 11,750 iron-
iron in combination with other micronutrients versus unfortified fortified participants and 9077 control participants, irrespective of
wheat, wheat flour fortified with iron in combination with other age and sex, were included in the Gera 2012 review which assessed
micronutrients versus fortified with the same micronutrients but the effect of iron fortification on Hb and serum ferritin and the
not iron, on Hb concentration, the risk of anaemia and ID among a prevalence of ID and anaemia. ID was defined in individual trials.
general population over two years of age. ID was defined by trialists, Participants receiving iron-fortified food showed an increase in
based on a biomarker of iron status. Compared with unfortified Hb concentration (WMD 4.20 g/L, 95% CI 2.80 to 5.60; 54 RCTs,
wheat flour, the intervention with wheat flour fortified with iron 19,161 participants) compared with control. The interventions also
alone increased Hb concentrations (MD 3.30 g/L, 95% CI 0.86 to reduced anaemia (RR 0.59, 95% CI 0.48 to 0.71; 33 trials, 13,331
5.74; 7 trials, 2355 participants; very low-certainty evidence) but participants; GRADE: not assessed) and ID (RR 0.48, 95% CI 0.38 to
found no difference in the reduction of anaemia (RR 0.81, 95% CI 0.62; 21 trials, 5765 participants, GRADE: not assessed) compared
0.61 to 1.07; 5 trials, 2200 participants; low-certainty evidence) or with control.
ID (RR 0.43, 95% CI 0.17 to 1.07; 3 trials, 633 participants; moderate-
certainty evidence). There was no difference in Hb concentration Sodium iron ethylenediaminetetraacetate (NaFeEDTA)-fortified soy
(MD 3.29 g/L, 95% CI -0.78 to 7.36; 3 trials, 384 participants; sauce versus non-fortified soy sauce
low-certainty evidence), the risk of anaemia (RR 0.95, 95% CI Sixteen RCTs and cluster-RCTS comprising 16,819 participants were
0.69 to 1.31; 2 trials, 322 participants; low-certainty evidence) included in the Huo 2015 systematic review, which examined the
and ID (RR 0.74, 95% CI 0.54 to 1.00; 3 trials, 378 participants; effect of NaFeEDTA-fortified soy sauce on anaemia prevalence in
moderate-certainty evidence), between wheat flour fortified with the Chinese population. The intervention led to an increase in
iron in combination with other micronutrients and unfortified Hb concentration (MD 8.81 g/L, 95% CI 5.96 to 11.67; 12 trials,
wheat. Wheat flour fortification with iron in combination with 8071 population, GRADE: not assessed) for participants receiving
other micronutrients, as compared to fortified with the same NaFeEDTA-fortified soy sauce compared with those receiving non-
micronutrients but not iron, reduced the risk of anaemia (RR fortified soy sauce. The review also reported a reduction in anaemia
0.24, 95% CI 0.08 to 0.71; 1 trial, 127 participants; very low- rates for participants receiving fortified soy sauce (OR 0.25, 95% CI
certainty evidence) and ID (RR 0.42, 95% CI 0.18 to 0.97; 1 trial, 127 0.19 to 0.35; 16 trials, 16,819 participants, GRADE: not assessed).
participants; very low-certainty evidence), but no difference was
found for Hb concentration (MD 0.81 g/L, 95% CI -1.28 to 2.89; 2
trials, 488 participants; low-certainty evidence).
(Review)
Informed decisions.
Double-fortified salt with iron and iodine versus control salt or iodine the benefits and harms of rice fortification with vitamins and
only fortified salt minerals (iron, vitamin A, zinc or folic acid) on micronutrient status
Fourteen RCTs, cluster-RCTs, and quasi-RCTs randomising over and health-related outcomes in the general population. Compared
45,995 participants of any age were included in the Ramírez- with unfortified rice or no intervention, fortification of rice with
Luzuriaga 2018 systematic review. This review assessed the impact iron (alone or in combination with other micronutrients) resulted in
of double-fortified salt with iron and iodine on biomarkers of iron increased Hb concentrations (MD 1.83 g/L, 95% CI 0.66 to 3.00; 11
status, the risk of anaemia and IDA. There was an increase in Hb trials, 2163 participants; low-certainty evidence) and reduced the
concentration for participants receiving double-fortified salt (MD risk of having anaemia (RR 0.72, 95% CI 0.54 to 0.97; 7 trials, 1634
3.01 g/L, 95% CI 1.79 to 4.24; 14 RCTs, 45,759 participants). Also, the children; low-certainty evidence) and ID (RR 0.66, 95% CI 0.51 to
intervention reduced the risk of anaemia (RR 0.84, 95% CI 0.78 to 0.84; 8 trials, 1733 participants; low-certainty evidence). The review
0.92; 10 trials, 42,103 participants; GRADE: not assessed) and IDA also reported no different reduction in diarrhoea (RR 3.52, 95% CI
(RR 0.37, 95% CI 0.25 to 0.54; 4 trials, 831 participants; GRADE: not 0.18 to 67.39; 1 trial, 258 children; very low-certainty evidence) and
assessed) for participants receiving double-fortified salt compared abdominal pain more than three days (RR 0.77, 95% CI 0.42 to 1.42;
with those receiving control salt. 1 trial, 234 children) for children consuming rice fortified with iron
or in combination with other micronutrients.
Another review, Yadav 2019, included 10 RCTs randomising over
3219 participants of all age and gender, and assessed the efficacy Fortification of rice with vitamin A (in combination with other
of double-fortified salt with iron and iodine as compared to iodine- micronutrients), compared with unfortified rice or no intervention,
fortified salt in improving iron nutrition status. The intervention increased Hb concentration (MD 10.00 g/L, 95% CI 8.79 to 11.21; 1
of double-fortified salt increased Hb concentrations (MD 0.44 g/L, trial, 74 participants; low-certainty evidence).
95% CI 0.16 to 0.71; 10 trials, GRADE: not assessed), and reduced Prevention
the risk of having anaemia (risk difference (RD) -0.16, 95% CI -0.26
to -0.06; 7 trials, 1526 participants, GRADE: not assessed) and ID Two reviews assessed micronutrient-fortified foods in mixed
(RD -0.20, 95% CI -0.32 to -0.08; 5 trials, 1306 participants; GRADE: populations (Das 2019b; Hess 2016).
not assessed). There was no difference in the reduction of IDA (RD
Micronutrient fortification versus placebo/no intervention
-0.08, 95% CI -0.28 to 0.11; GRADE: not assessed) for participants
consuming double-fortified salt. Forty-three RCTs, cluster-RCTs, quasi-randomised trials, CBA
studies, and ITS studies comprising 19,585 healthy men, women
Iron-fortified flour versus control
and children were included in the Das 2019b systematic review. This
One hundred and one controlled trials and before-after studies review evaluated the impact of micronutrient fortification versus
that aimed to assess the effectiveness of iron-fortified flour on iron placebo/no intervention on serum Hb level, the risk of anaemia, IDA
status of women, children, and infants/toddlers were included in and ID. IDA was defined as Hb < 11 g/dL with serum ferritin < 15
the systematic review by Sadighi 2019. This review reported that μg/L. There was an increase in serum Hb concentration (MD 3.01
iron-fortified flour led to increases of Hb concentration (MD 2.63 g/L, 95% CI 2.14 to 3.87; 20 trials, 6985 participants, low-certainty
g/L, 95% CI 1.31 to 3.95; 46 trials, 10,353 participants; GRADE: not evidence) and a decrease in the risk of anaemia (RR 0.68, 95% CI
assessed), and decreases in prevalence of anaemia (MD −8.1%, 0.56 to 0.84; 11 trials, 3,746 participants; low-certainty evidence),
95% CI −11.7% to −4.4%; 27 trials, 6950 participants; GRADE: not IDA (RR 0.28, 95% CI 0.19 to 0.39; 6 trials, 42,189 participants;
assessed), ID (MD −12.0%, 95% CI −18.9% to −5.1%; 23 trials, 5371 low-certainty evidence) and ID (RR 0.44, 95% CI 0.32 to 0.60; 11
participants; GRADE: not assessed), and IDA (MD −20.9%, 95% CI trials, 3,289 participants; low-certainty evidence) for participants
−38.4% to −3.4%; 15 trials, 4260 participants, GRADE: not assessed). receiving micronutrient fortification compared with placebo/no
intervention.
Wheat flour fortified with folic acid and other micronutrients versus
unfortified wheat flour Fortified condiments or noodles versus non-fortified condiments or
noodles
Five RCTs, non-RCTs, and ITS studies including 1182 general
population participants aged over two years (including Fourteen RCTs and cluster-RCTS randomising over 8674 children
pregnant and lactating women) were included in the Tablante and adults aged 5 to 50 years were included in the systematic
2019 systematic review. This review evaluated the health benefits review by Hess 2016. This review investigated the impact of
and safety of folic acid fortification on wheat and maize flour micronutrient-fortified condiments and noodles on Hb, anaemia
(alone or in combination with other micronutrients), compared and functional outcomes. The prevalence of anaemia was reported
with wheat or maize flour without folic acid, on folate status and as 46% at baseline in this review. There was a positive effect of the
health outcomes in the overall population. There were no effects of intervention on Hb concentration (WMD 6.80 g/L, 95% CI 5.10 to
fortified wheat flour flatbread, compared to unfortified wheat flour 8.50; 13 trials, 8845 participants; GRADE: not assessed). Participants
flatbread, on Hb concentrations (MD 0.00 g/L, 95% CI -2.08 to 2.08; receiving fortified foods compared with those receiving non-
1 trial, 334 children; low-certainty evidence), and anaemia (RR 1.07, fortified foods showed a reduction in the prevalence of anaemia (RR
95% CI 0.74 to 1.55; 1 trial, 334 children; low-certainty evidence). 0.59, 95% CI 0.44 to 0.80; 10 trials, 5498 participants, GRADE: not
assessed).
Improving dietary diversity and quality (one review)
Seventeen RCTs, cluster-RCTs, quasi-RCTs, non-RCTs, CBA studies,
and ITS studies, including 10,483 general population participants Food prepared in iron pots
older than two years of age (including pregnant women) were
Prevention
included in the Peña-Rosas 2019 systematic review which assessed
(Review)
Informed decisions.
Three RCTs comprising 784 children aged at least four months reviews and were found to increase Hb levels and reduce anaemia.
were included in the Geerligs 2003 systematic review. The review MNP (3 reviews) compared with placebo or no intervention
assessed the effect of preparing food cooked in cast iron pots on increased Hb levels (2 reviews, moderate-certainty evidence; 1
Hb concentrations. In this review, the results of the three RCTs were review, GRADE not assessed) and reduced the risk of anaemia
reported separately due to high heterogeneity. Two RCTs found (2 reviews, moderate-certainty evidence; 1 review, outcome not
higher Hb levels in children eating food prepared in cast iron pots reported). This intervention also reduced the risk of IDA by
(MD 13.00 g/L, 2 RCTs) in non-malaria-endemic areas. Another trial 57% (moderate-certainty evidence) and ID by 51% (high-certainty
reported no difference in Hb concentrations (MD 0.20 g/L) between evidence). MNP supplementation may result in a small increase
children aged 1 to 11 years eating food prepared in cast iron pots in the incidence of diarrhoea (4%; moderate-certainty evidence)
compared with children eating food prepared in non-cast iron pots, but not recurrent diarrhoea. Comparing MNP supplementation
as well as for children older than 12 years (MD 3.00 g/L). with iron supplementation, no differences in Hb levels (low-
certainty evidence) and anaemia (low-certainty evidence) were
DISCUSSION observed, but MNP supplementation reduced the incidence of
adverse effects (incidence of diarrhoea, vomiting, staining of teeth
This overview of reviews identified 75 systematic reviews assessing and stool discolouration). One review investigating the effect of
the effects of various interventions to prevent or control anaemia home fortification of complementary foods found no differences in
at different stages of life. Half of the included reviews were rated as Hb levels, anaemia and diarrhoea when compared with iron drops,
being of high methodological quality and the remaining reviews as but increases in Hb levels, and 46% reduction in anaemia and a 56%
medium quality. reduction in ID when compared with placebo or no intervention.
Summary of main results Improving dietary diversity and quality
Of the 75 included systematic reviews, 13 reviews included infants Improving dietary diversity and quality in infants was assessed in
aged 6 months to 23 months at the start of the interventions, eight three systematic reviews. Food-based strategies (red meat, fortified
reviews included children 2 years to 10 years of age, four reviews cow's milk, beef, fortified food with fish powder) versus control
included adolescents aged 11 to 18 years, five reviews included showed no difference in Hb levels between the groups, while
non-pregnant women between 19 and 49 years of age, 23 reviews caterpillar cereal increased Hb levels and reduced IDA prevalence.
included pregnant women aged 15 to 49 years, and 22 reviews The intervention 'supplementary feeding alone or in combination
included mixed populations. We did not identify any reviews that with added micronutrient' was associated with an increase in Hb
included only older adult women aged 50 to 65 years or above levels in infants.
or only adult men aged 19 to 65 years or above. Few reviews
reported on anaemia and malaria prevalence. GRADE assessments Preschool and school-aged children (aged 2 to 10 years)
were provided in only 33 out of 75 reviews. These varied between
Supplementation
high and very low, meaning we are not certain about the effects
of nutrition-specific interventions for controlling anaemia and iron Four reviews assessed supplementation interventions for
deficiency. preschool and school-aged children. Three of them investigated the
effects of iron supplementation. Daily oral iron supplementation
Infants (aged 6 to 23 months) increased Hb levels and reduced the risk of anaemia by 50%,
Supplementation IDA by 88% and ID by 79% compared with placebo or control.
There were no differences in adverse effects (gastrointestinal upset,
Of the six systematic reviews that assessed supplementation constipation, and vomiting). Intermittent iron supplementation
interventions for infants, four investigated the effect of iron alone or with other nutrients increased Hb levels (low-certainty
supplementation. Oral iron (alone or in combination with evidence) and reduced the risk of anaemia by 49% (moderate-
co-interventions) supplementation compared with placebo, no certainty evidence) and ID by 76% (low-certainty evidence)
treatment or other interventions showed a positive effect on Hb compared with placebo or no intervention. No differences in side
levels (1 review, moderate-certainty evidence). The intervention effects were observed between the groups. Comparing intermittent
also reduced the risk of anaemia by 31% (low-certainty evidence), iron supplementation with daily iron supplementation, no
IDA by 80% (high-certainty evidence) and ID by 78% (high-certainty differences were observed between the groups for the outcomes
evidence). Adverse effects were less frequently reported, but an of Hb levels (low-certainty evidence), diarrhoea, and any side
increase in vomiting was reported in one review, while the other effects. However, children receiving intermittent iron showed a 23%
reviews did not see any differences in adverse effects between the increased risk of anaemia (low-certainty evidence), 30% increased
intervention and control groups. One review investigated the effect risk of ID (very low-certainty evidence) compared with daily iron.
of zinc supplementation and found no clear evidence of a difference Zinc supplementation for preschool and school-aged children was
in Hb levels between zinc supplementation and placebo. LNS investigated in one review. Zinc supplementation compared with
plus complementary feeding resulted in a reduction of anaemia no zinc supplementation showed no differences in Hb levels,
compared with no intervention or MNP (low-certainty evidence), prevalence of anaemia, prevalence of ID or ≥ 1 side effect. However,
but there was no evidence of difference in adverse effects between the intervention increased the risk of vomiting episodes by 68%
the groups (moderate-certainty evidence). and increased risk of ≥ 1 vomiting episode by 29% (high-certainty
evidence). Children receiving zinc plus iron showed higher Hb levels
Fortification and a 22% reduction in the prevalence of anaemia and an 88%
Six systematic reviews assessed fortification intervention for reduction in the prevalence of ID compared with zinc alone.
infants. Iron-fortified milk or cereals was investigated in two
(Review)
Informed decisions.
Fortification Improving dietary diversity and quality

Four reviews assessed fortification interventions. MMN-fortified None of the included reviews assessed interventions to improve
beverages for preschool and school-aged children increased Hb dietary diversity and quality for adolescent children.
levels (moderate-certainty evidence) and reduced the risk of
anaemia by 37% (moderate-certainty evidence), the risk of ID by Non-pregnant women of reproductive age (aged 19 to 49
68% (moderate-certainty evidence), and the risk of IDA by 87% years)
(low-certainty evidence) compared with children in the control Supplementation
group. Comparing fortified dairy products and cereal food with
no fortification showed no clear evidence of a difference in Five systematic reviews assessed supplementation interventions
Hb levels, risk of anaemia, and adverse events, while fortified for non-pregnant women. Iron therapy (oral, intravenous (IV),
dairy products and cereal food reduced the risk of IDA by 62% intramuscular (IM)) increased Hb levels compared with control
(very low-certainty evidence), and ID by 38% (very low-certainty but no differences were observed for the outcomes of anaemia,
evidence). Children receiving zinc-fortified food compared with gastrointestinal intolerance, nausea, constipation or diarrhoea.
children receiving a regular diet or unfortified food showed no Compared to placebo, iron folic acid supplementation reduced the
differences in Hb levels. Point-of-use fortification of foods with iron- incidence of anaemia by 34% (very low-certainty evidence). Also,
containing MNP increased Hb levels (low-certainty evidence) and weekly use of this intervention reduced the incidence of anaemia
reduced the prevalence of anaemia by 34% (moderate-certainty by 30% (very low-certainty evidence), and daily use reduced it by
evidence), and ID by 65% (moderate-certainty evidence) compared 51% (very low-certainty evidence). In another review, daily iron
with no intervention or placebo. No difference was observed for IDA supplementation with or without co-intervention (folic acid or
and diarrhoea (low-certainty evidence). vitamin C) resulted in increased Hb levels (high-certainty evidence),
a 61% reduced risk of anaemia (moderate-certainty evidence), a
Improving dietary diversity and quality 35% reduced risk of IDA, and a 38% reduced risk of ID (moderate-
certainty evidence) compared with no iron supplementation. The
None of the included reviews assessed interventions to improve
intervention showed no differences between the groups for any
dietary diversity and quality for preschool and school-aged
adverse side effects. In the review that compared IV iron to oral
children.
iron, IV iron increased Hb levels. Another review assessed MMN
Adolescent children (aged 11 to 18 years) supplementation, but reported no outcomes related to anaemia.
Supplementation Fortification
Four reviews assessed supplementation interventions for None of the included reviews assessed fortification interventions
adolescent children. Intermittent iron supplementation alone or for non-pregnant women of reproductive age.
with other vitamins and minerals increased Hb levels (moderate-
certainty evidence) and reduced the risk of anaemia by 35% (low- Improving dietary diversity and quality
certainty evidence) compared with no supplementation or placebo. None of the included reviews assessed interventions to improve
There were no differences between intervention and control groups dietary diversity and quality for non-pregnant women of
for the outcomes of IDA (low-certainty evidence), ID (low-certainty reproductive age.
evidence), or any adverse effects (moderate-certainty evidence).
Comparing this intervention to daily iron supplementation, there Pregnant women of reproductive age (aged 15 to 49 years)
were no differences in Hb levels (low-certainty evidence), incidence
of anaemia (moderate-certainty evidence), or ID (very low-certainty Supplementation
evidence), but there was a 79% reduction in the risk of adverse Twenty-two reviews assessed supplementation interventions for
effects (low-certainty evidence). Iron supplementation, iron plus pregnant women. Eleven reviews assessed iron supplementation.
folic acid and iron plus antimalarial supplementation increased In one review, daily iron supplementation with or without folic
Hb levels for children with or without anaemia compared with acid increased Hb levels in the third trimester or at delivery and
placebo. These interventions reduced the incidence of anaemia; in the postpartum period. Also, the risk of anaemia was reduced
iron supplementation reduced by 37%, iron plus folic acid reduced by 50%, IDA by 60%, and ID in the third trimester or at delivery by
by 51%, and iron plus antimalarial supplementation reduced by 41%. The comparison, iron only versus no iron or placebo resulted
56%. Iron supplementation with or without folic acid increased Hb in increased Hb levels in the third trimester or at delivery and
levels (low-certainty evidence), but there was no clear evidence of in the postpartum period, and reduced the risk of anaemia by
an effect in the incidence of anaemia (low-certainty evidence). Also, 44% and ID by 41%. Iron with folic acid versus no iron and folic
comparing MMN to no fortification, there was no clear evidence acid supplements also increased Hb levels and reduced the risk of
of an effect in Hb levels (low-certainty evidence). Another review anaemia by 56% in the third trimester or at delivery. In another
compared micronutrient supplementation with control and found review, iron supplementation reduced the risk of anaemia at term
an increase in Hb levels and a 31% reduction in the risk of anaemia by 69% (moderate-certainty evidence) and IDA at term by 56%. Any
(moderate-certainty evidence) in the intervention group. supplement containing iron compared with the same supplement
without iron or no treatment or placebo increased Hb levels at or
Fortification near term and postpartum, and reduced the risk of anaemia by
None of the included reviews assessed fortification interventions 70% (low-certainty evidence), IDA by 67%, ID by 57% (low-certainty
for adolescent children. evidence) at or near term, and severe anaemia postpartum by 96%.
In the same review, iron and folic acid versus the same supplement
without iron and folic acid showed an increase in Hb levels at or
(Review)
Informed decisions.
near term and postpartum, and a reduction in the risk of anaemia evidence) for the fortification intervention compared with MMN
at or near term by 66% (moderate-certainty evidence), ID at or supplementation.
near term by 76% (low-certainty evidence), and severe anaemia at
any time during second and third trimester by 82% (low-certainty Improving dietary diversity and quality
evidence) and postpartum by 95%, but an increase in the risk of side None of the included reviews assessed interventions to improve
effects (moderate-certainty evidence). In another review assessing dietary diversity and quality for pregnant women of reproductive
intermittent iron supplementation, the intervention increased the age.
risk of anaemia at or near term by 66% and ID by 138%, and reduced
the risk of side effects by 44% (very low-certainty evidence), but had Mixed population (all ages)
no effect on Hb levels and IDA. Five reviews investigating different
iron treatments for pregnant women with IDA, found that IV iron Supplementation
compared with oral iron or IM iron increased Hb levels, as did Of the nine reviews assessing supplementation interventions for
daily versus weekly oral iron and different oral iron doses, and mixed populations, six reviews investigated the effect of iron
oral iron versus placebo. Another review assessed various different supplementation. Iron supplementation versus placebo or control,
treatments for IDA in pregnancy and found positive effects on Hb as investigated in three reviews, increased Hb levels in healthy
levels for oral iron versus placebo, oral iron plus vitamin A versus adults, children and elderly people, but there was no difference
placebo, IV iron versus oral iron, IM iron versus oral iron (with or between the groups for adverse events. Iron with MMN increased
without folic acid), daily versus oral iron once or twice per week, Hb levels in children compared with placebo or no treatment and
oral iron twice per week versus once per week, IV iron sucrose 200 slightly increased Hb levels compared with iron supplementation
mg or 500 mg versus IM, and IV iron plus oral iron versus oral iron. alone. Another review assessing an iron intervention found
The same review showed a reduction in the risk of anaemia during an increase in Hb levels for children with anaemia or IDA
the second trimester of 62% for oral iron versus placebo and 96% receiving iron supplementation and a decrease in Hb levels for
for oral iron plus vitamin A versus placebo, and an improvement in those receiving dietary interventions. The same review showed
the outcome 'not anaemic at term' for IM iron versus oral iron (with lower prevalences of anaemia for participants receiving iron
or without vitamin C and folic acid). IV versus oral iron for pregnant supplementation compared with fortification, and in adolescents
women with IDA was assessed in four reviews and was found to and adults there was no difference in Hb levels between the
increase Hb levels at the end of treatment and reduce the risk of dietary plan group and the iron supplementation group. One review
adverse events. found an increased risk (132%) of gastrointestinal side effects for
participants receiving oral iron compared with placebo. The same
Two reviews assessed vitamin A supplementation. Vitamin A review showed an increase in Hb levels for IV iron compared with
supplementation alone versus placebo or no intervention resulted oral iron supplementation and an increased risk of gastrointestinal
in a 36% reduced risk of maternal anaemia (moderate-certainty side effects. Compared with placebo, vitamin B12 or folic acid
evidence). Vitamin A supplementation versus placebo or other
supplementation in an elderly population showed no differences in
micronutrient increased maternal Hb levels (moderate-certainty
Hb levels between the groups. There was no difference in Hb levels
evidence), and reduced the risk of maternal anaemia by 19%,
between the groups comparing vitamin D supplementation with
but not severe anaemia (low-certainty evidence). Two reviews
placebo.
assessed folic acid supplementation during pregnancy and found
no difference in pre-delivery Hb levels and anaemia compared Fortification
with no folic acid supplementation. Three reviews assessed MMN
supplementation with iron and folic during pregnancy and found Twelve reviews assessed fortification interventions for mixed
no effects on maternal Hb concentration (low-certainty evidence) populations. Iron fortification of food resulted in an increase in
and anaemia (moderate to high-certainty evidence) in the third Hb levels and reduced the risk of anaemia by 41% and ID by
trimester, compared with iron and folic supplementation alone. 52% compared with control. MMN fortification compared with
However, MMN with iron and folic acid compared with placebo placebo or no intervention showed in an increase in Hb levels
reduced the risk of anaemia by 34%. One review assessing the effect and reduced the risk of anaemia, IDA, and ID. However, wheat or
of calcium supplementation found no evidence of a difference maize flour fortified with iron plus other vitamins and minerals
in anaemia when compared with placebo or no treatment. The versus unfortified wheat or maize flours showed no effect on Hb
supplementation with oral bovine lactoferrin increased Hb levels levels, anaemia, IDA and ID. Rice fortification with iron alone or
(low-certainty evidence) and reduced gastrointestinal side effects in combination with other micronutrients resulted in an increase
compared with oral ferrous iron preparations. One review assessing in Hb levels and decreased the risk of anaemia and ID compared
the effect of LNS found an increase in the prevalence of anaemia with unfortified rice or no intervention. Another review assessed
when compared with IFA or MMN treatment, with no difference in NaFeEDTA-fortified soy sauce in a Chinese population and found
hospitalisation episodes. an increase in Hb levels and a 75% reduction of anaemia rates
compared with non-fortified soy sauce. Double-fortified salt with
Fortification iron and iodine increased Hb levels and also reduced the risk
of anaemia by 16% and IDA by 63% compared with control
Two reviews assessed MMN fortification for pregnant women. Non-
salt. Fortified condiments or noodles compared with non-fortified
dairy MMN-fortified beverages improved Hb levels for pregnant
condiments or noodles increased Hb levels and reduced the risk of
women compared with iso-caloric non-fortified beverages. MNP for
anaemia by 41%.
point-of-use fortification of food reduced Hb levels at 32 weeks'
gestation and increased the risk of anaemia compared with iron
and folic acid supplementation. No differences were observed in
Hb levels at term or near term and anaemia (very low-certainty
(Review)
Informed decisions.
Improving dietary diversity and quality not include any recent controlled trials assessing the effects of
supplementation and fortification to prevent or correct anaemia.
One review assessed the effects of foods prepared in iron pots, and
Additionally, only 37% of the included reviews actively reported
found higher Hb levels in children with low-risk malaria status in
adverse events. This may affect the completeness of the evidence,
two trials, but another trial found no difference when compared
as conclusions can only be drawn based on the available data.
with consuming food prepared in non-cast iron pots in a high-risk
malaria endemicity mixed population. Adverse events have not This overview of reviews summarised the demonstrated effects
been reported in the review. Using iron pots may have prophylactic and the certainty of the evidence of nutrition-specific interventions
benefits for malaria endemicity low-risk populations. across reviews and participant groups, including infants, preschool
or school-aged children, adolescent children, non-pregnant adult
Overall completeness and applicability of evidence women aged between 19 and 49 years, pregnant women, and mixed
The objective of this overview of reviews was to summarise populations. Where systematic reviews were similar in relation
the benefits or harms of nutrition interventions for preventing to research question, participants and interventions, we chose
and controlling anaemia in anaemic or non-anaemic, apparently the most comprehensive review. The results of this summary can
healthy populations throughout the life cycle. Anaemia prevalence help policymakers and healthcare professionals to determine the
fluctuates according to various factors, including age, living implementation and evaluation of nutrition-specific interventions.
area, sex and socioeconomic status. This overview of reviews We also believe this overview of reviews highlights areas that need
summarised extensive evidence on the effects of three types of further research.
interventions: 1) supplementation for infants (6 reviews), preschool
and school-aged children (4 reviews), adolescent children (4 Aside from nutritional factors, other non-nutritional factors, such
reviews), non-pregnant women (5 reviews), pregnant women as inflammation, infections or genetic disorders can cause iron
(22 reviews), and mixed populations (9 reviews); 2) fortification deficiency or anaemia. Therefore, interventions need to address
for infants (5 reviews), preschool and school-aged children (4 the various causes of the condition in an a multisectoral approach.
reviews), pregnant women (1 review), and mixed populations (12 The treatment or prevention of non-nutritional anaemia has
reviews); and 3) improving dietary diversity and quality for infants been discussed in related Cochrane Reviews which complement
(2 reviews), preschool and school-aged children (1 review), and our overview review. Gordon 2021 compared different forms
mixed populations (1 review). In total, we included 75 systematic of iron administration (IV, oral) to treat IDA in people with
reviews, which included one or more of our primary outcomes inflammatory bowel disease. Another review investigated the
(Hb concentration, anaemia or IDA) and secondary outcomes (ID, effects of micronutrient supplementation in pregnant women with
severe anaemia, or adverse effects). The number of trials included HIV infection, and in this context assessed maternal haematological
in these systematic reviews ranged from 2 to 90 trials, and the parameters (Siegfried 2012). In an overview review of Cochrane
number of participants ranged from 52 to over 310,000. At least 67 Reviews, Fortin 2018 assessed red blood cell transfusion to treat
of the included reviews were conducted in low- and middle-income or prevent complications in sickle cell disease, an inherited blood
countries, and we synthesised the data from numerous countries of disorder which results in anaemia due to abnormal red blood cells.
differing cultural and economic backgrounds.
Certainty of the evidence
Although we comprehensively summarised the data from various We assessed the quality of the included reviews using the
systematic reviews, there was a limited number of systematic AMSTAR tool (Shea 2007a; Shea 2007b; Shea 2009), which is
reviews regarding some factors. First, none of the systematic the recommended approach for systematic reviews. Of these,
reviews included adult men aged over 19 years and older adult 26 Cochrane Reviews were of high quality, because they all
women aged over 50 years. Thus, we could not conclude the followed a similar and prescribed process (Abe 2016; Buppasiri
benefits or harms of nutrition interventions for theses populations. 2015; Das 2018; Das 2019a; Das 2019b; Suchdev 2020; De-Regil
However, 42% of children younger than five years of age, 2011; De-Regil 2015; De-Regil 2017; Garcia-Casal 2018; Fernández-
30% of non-pregnant women, and 40% of pregnant women Gaxiola 2019; Keats 2019; Lassi 2013; Kristjansson 2015; Low 2016;
aged 15 to 49 years were estimated as anaemic (WHO 2020a; Mayo-Wilson 2014a; McCauley 2015; Neuberger 2016; Peña-Rosas
WHO 2020b). This overview provided a comprehensive summary 2015a; Peña-Rosas 2015b; Peña-Rosas 2019; Reveiz 2011; Rumbold
of the effects and harms of supplementation, fortification, 2015; Shi 2015; Suchdev 2015; Tablante 2019). Systematic reviews
and interventions to improve dietary diversity and quality for should be conducted using a rigorous method to minimise the
these high-risk populations. Second, most systematic reviews potential for bias in the review process (Higgins 2021). However,
focused on supplementation (50 reviews) and fortification (22 some reviews had specific methodological limitations that could
reviews) interventions; only three systematic reviews focused on create bias: conflict of interest disclosure not stated (56 reviews),
interventions to improve dietary diversity and quality. Third, as publication bias not assessed (38 reviews), included and excluded
of June 2021, reviews included in this overview were conducted trials not listed (35 reviews), and review protocol not provided
between 2003 and 2019. Even though Cochrane recommends that (21 reviews) (Table 15; Table 16; Table 17; Table 18; Table 19;
Cochrane Reviews should be updated periodically depending on Table 20). Although supplementation trials might be sponsored by
the continuing importance of the review question, sufficiency of commercial companies, 76% of included systematic reviews did
new evidence or new methods, 12 of 20 included Cochrane Reviews not disclose their conflict of interest. In addition, the AMSTAR tool
conducted their searches before July 2015 (Buppasiri 2015; De- was developed to assess the methodological quality of systematic
Regil 2011; Kristjansson 2015; Lassi 2013; Mayo-Wilson 2014a; reviews using the reports of systematic reviews (Shea 2007a; Shea
McCauley 2015; Peña-Rosas 2015b; Reveiz 2011; Rumbold 2015; Shi 2007b; Shea 2009), but not the actual undertaking or conduct
2015; Suchdev 2015; Suchdev 2020); we found some new relevant of the review process (Faggion 2015; Wegewitz 2016). Therefore,
studies that had been published since 2015. These reviews did the assessment of methodological quality highly depends on the
(Review)
Informed decisions.
accurate and thorough reporting in the systematic review. The make some interesting updates to the results in further versions
results presented in this overview of reviews should be used with of this overview of reviews. Furthermore, we highly encourage
caution, considering the risks of these potential biases. international readers to provide feedback on the interpretation of
the results, in order to improve future updates of this review.
All included reviews assessed the risk of bias in the included trials
using several assessment tools such as the Cochrane RoB 1 tool Agreements and disagreements with other studies or
(Higgins 2011), the Jadad level-of-evidence score for RCTs (Jadad reviews
1996), and the Modified Critical Appraisal Skills Programme (CASP)
tool (CASP 2013). About 70% of the included reviews used the We did not identify other overview reviews or network meta-
Cochrane RoB 1 tool (Higgins 2011). They included a variety of trials, analyses assessing nutrition-specific interventions for preventing
varying between low and high risk of bias (Table 3; Table 4; Table 5; and controlling anaemia at any stage of life. In this overview
Table 6; Table 7; Table 8). These reviews included individual trials at of reviews, one possible explanation for the agreements and
high risk of bias due to no or insufficient description of methods for disagreements with other reviews is the differences in trial settings,
random sequence generation and allocation concealment, as well or methodological quality. For example, a pooled analysis of a
as lack of blinding. Cochrane Review assessing the effectiveness of home fortification
of foods with MNPs for health and nutrition in children under two
Of the 75 included reviews, 33 assessed the certainty of the years of age shows there may be an increase in Hb concentration
evidence for relevant outcomes using the GRADE approach (Aaron and likely reduction in anaemia and ID (Suchdev 2020). The findings
2015; Abu Hashim 2017; Basutkar 2019; Bhutta 2012; Das 2018; of that review agree with evidence from a systematic review and
Das 2019a; Das 2019b; De-Regil 2011; De-Regil 2017; Eichler meta-analysis in which a MNP intervention likely increased Hb
2019; Field 2020; Garcia-Casal 2018; Fernández-Gaxiola 2019; levels (SMD 0.98, 95% CI 0.55 to 1.44; 9132 children), and reduced
Haider 2011; Imdad 2012; Lassi 2020; Low 2016; Mayo-Wilson anaemia and ID by 34% and 57%, respectively (Salam 2013).
2014a; McCauley 2015; Petry 2016b; Peña-Rosas 2015a; Peña-Rosas However, the findings from both reviews on the adverse effect of
2015b; Peña-Rosas 2019; Qassim 2019; Radhika 2019; Salam 2013; the intervention on the incidence of diarrhoea, disagreed; Salam
Salam 2016; Salam 2020; Suchdev 2015; Suchdev 2020; Tablante 2013 found that MNPs likely increase the incidence of diarrhoea
2019; Thompson 2013; Thorne-Lyman 2012). Although six reviews by 4%, whereas Suchdev 2020 did not find any association with
planned to assess the certainty of the evidence, they did not assess the adverse effect, diarrhoea. These discordant findings are due to
it for relevant outcomes (Abe 2016; Buppasiri 2015; De-Regil 2015; differences in settings, where provision of the same intervention
Keats 2019; Kristjansson 2015; Rumbold 2015). GRADE is a rating from one setting to another might influence the effectiveness of
of the certainty that the true effect lies on one side of a particular the intervention when conditions and socioeconomic status are
threshold or in a particular range. High-certainty evidence indicates culturally different. Though both reviews restricted the sites to
a low likelihood that the effect will be different enough from what low- and middle-income countries, Suchdev 2020 included trials
the research found to affect a decision (Hultcrantz 2017). In this conducted in anaemia- and malaria-prevalent settings, whereas
overview of reviews, the certainty of the evidence for the estimates this was not described in Salam 2013. Furthermore, Suchdev 2020
of relevant outcomes ranged between very low (for example, the included individual RCTs, cluster-RCTs and quasi-RCTs in their
effects of MNP for the point-of-use fortification of semi-solid foods review, whereas Salam 2013 included only RCTs and cluster-RCTs.
for pregnant women; Suchdev 2015) and high (for example, for the
effect of daily oral iron supplementation for non-pregnant women There were also similar findings in other interventions for different
to improve Hb; Low 2016). In general, the certainty of the evidence types of population. For example, daily iron supplementation
varied between low and moderate. compared with placebo or control resulted in an increase in Hb
concentration for infants aged 6 to 23 months (Petry 2016b),
Potential biases in the overview process preschool and school children aged 2 to 10 years (Low 2013),
non-pregnant women aged 19 to 49 years (Low 2016), pregnant
We considered several potential biases at all stages of the overview women aged 15 to 49 years (Haider 2013), and a mixed population
process and made efforts to reduce them in different ways. For of elderly people over 64 years old (Tay 2015). The intervention
example, we included outcomes in the search strategy in order to may decrease anaemia by 41% in infants (Petry 2016b), 50%
limit the number of references to the relevant reviews for this broad in preschool and school-aged children (Low 2013), 41% in non-
research question. At least two review authors independently pregnant reproductive-aged women (Low 2016), and 44% in
assessed the reviews for inclusion according to the eligibility the third trimester or at delivery (Haider 2013); reduced IDA
criteria, extracted data and assessed the quality of the included by 80% in infants (Petry 2016b), 88% in preschool and school-
reviews using AMSTAR (Shea 2007a; Shea 2007b; Shea 2009). We aged children (Low 2013), 35% in non-pregnant reproductive-aged
resolved disagreements through discussion with a third review women (Low 2016), and 63% in the third trimester or at delivery
author, where necessary. We included both Cochrane Reviews and (Haider 2013); and reduced ID by 78% in infants (Petry 2016b),
non-Cochrane Reviews that included individual RCTs, cluster-RCTs, 79% in preschool and school-aged children (Low 2013), 38% in
quasi-RCTs, controlled before-after trials or cross-over trials, in non-pregnant reproductive-aged women (Low 2016), and 41%
order to limit the risk of bias that may be reported by observational in the third trimester or at delivery (Haider 2013). Furthermore,
data and narrative reviews. We considered systematic reviews there was no evidence of a difference in any adverse side effect
that assessed the methodological quality of the included trials, (e.g. diarrhoea, constipation, or vomiting) of the intervention,
both with and without meta-analyses, but did not include meta- regardless of the types of trial participants or their ages.
analyses without systematic reviews. We listed 18 eligible ongoing
systematic reviews in Appendix 1 to be included in future updates
of this overview of reviews. Therefore, we would like to check
all related findings of these ongoing reviews, as these may
(Review)
Informed decisions.
AUTHORS' CONCLUSIONS anaemia within one population. Furthermore, this review did
not include populations at risk of anaemia due to acute or
Implications for practice chronic infections, acquired bone marrow disorders, inflammation
or inherited anaemia. However, treatment and prevention of
We carefully summarised the effects of supplementation
infectious diseases (e.g. helminth infection or malaria) is important
interventions, fortification interventions and interventions to
and should be addressed, in addition to the interventions
improve dietary diversity and quality in various different
described in this overview review. Programmes need to include
populations in order to treat or prevent anaemia. In most
nutrition-specific and nutritional-sensitive interventions and
cases, the population consisted of a mix of anaemic and non-
involve multiple sectors to tackle the condition. Furthermore,
anaemic participants, and anaemia and malaria prevalence in the
population characteristics (e.g. age, baseline anaemia status and
setting were rarely reported in included reviews. Supplementation
micronutrient deficiencies) as well as local conditions (e.g. anaemia
interventions in particular have been intensively studied in infants,
and malaria prevalence) need to be carefully assessed in order to
preschool and school-aged children, pregnant women, and mixed
choose the most suitable intervention.
populations. Daily iron supplementation (12.5 mg to 15 mg iron/
day) versus no supplementation, no treatment, or placebo has the Implications for research
potential to increase Hb levels in infants aged 6 to 23 months by
4.1 g/L to 7.22 g/L, and reduce the risk of anaemia by 39% to 41% We identified several systematic reviews focusing on interventions
and IDA by 80% to 86%. In preschool and school-aged children for infants, preschool and school-aged children, adolescent
aged 2 to 10 years, daily (5 mg/day to 400 mg/day) or intermittent children, non-pregnant and pregnant women of reproductive age,
(7.5 mg/week to 200 mg/week) iron supplementation increased Hb and mixed populations. Additionally, we identified only a small
levels by 5.2 g/L to 8.4 g/L, and reduced the risk of anaemia by number of reviews assessing the effects of different interventions
49% to 50% and IDA by 88%. In non-pregnant women, daily oral to prevent or treat anaemia in adolescent children, non-pregnant
iron (1 mg/day to 300 mg/day) versus no iron supplementation women, women aged 50 to 65 years, and men aged 19 to 65 years.
also increased Hb levels by 4.0 g/L to 5.3 g/L, and reduced the Future trials should focus on these specific populations in order
risk of anaemia by 61% and IDA by 38%. For pregnant women, this to assess the effects of different interventions to treat or prevent
intervention (10 mg/day iron to 300 mg/day iron) increased Hb anaemia. Furthermore, in any age group, only a limited number
levels in the third trimester or at delivery by 4.5 g/L to 13.4 g/L, of reviews assessed interventions to improve dietary diversity and
and reduced the risk of anaemia by 50% to 70% and IDA by 56% quality. These interventions should be prioritised to create a long-
to 67%. Iron plus folic acid versus no iron and folic acid or placebo lasting and sustainable impact on iron status and anaemia at
had a greater impact on the increase of Hb levels at or near term any stage of life. Research efforts should be focused on different
(10.41 g/L to 16.13 g/L). In addition, vitamin A supplementation types of interventions to increase the variety of foods and dietary
(3333 IU/day to 444,000 IU/day) can improve Hb levels by 3.5 quality as well as take into account the special requirements of
g/L and reduce the risk of anaemia by 19% to 36%. For mixed different populations. Most of the included reviews did not report
populations, oral iron (5 mg/day to 120 mg/day) versus placebo adverse events which could have led to selection, publication,
or control resulted in an increase in Hb levels (3.5 g/L to 7.4 g/L). and reporting bias in this overview review. There is also a need
Intermittent and daily iron supplementation showed no differences for trials to assess adverse events and side effects as many trials
in Hb levels and risk of anaemia in preschool and school-aged did not evaluate the safety of the interventions. Future research
children and adolescent children, which provides the opportunity should also focus on understanding how effects of interventions
to use either regimen for these populations. However, in pregnant differ by the type of the intervention or characteristics of the
women, intermittent iron supplementation increased anaemia at population or setting. More than half of the included reviews did
or near term and ID, indicating that intermittent regimen may not perform any GRADE assessment. Therefore, future systematic
pose a risk to pregnant women. Food fortification increased Hb reviews should be conducted well and assess the certainty
levels and reduced anaemia. MNP fortification led to increases in the evidence of relevant outcomes. In addition to further
in Hb levels and reductions in the risk of anaemia and IDA in systematic reviews, non-nutritional interventions and programmes
infants, preschool and school-aged children and pregnant women, including multiple interventions (e.g. nutrition-specific and
compared with no intervention or placebo. No differences were nutrition-sensitive interventions implemented in parallel) should
found when comparing MNP with iron supplementation, indicating be considered and evaluated due to the multifactorial causation of
that MNP or iron supplementation can be used to improve anaemia.
Hb levels and anaemia. Interventions aimed to improve dietary
diversity and quality were mixed and largely depended on the ACKNOWLEDGEMENTS
particular intervention and population. MNP or iron fortification of
We thank Juan Pablo Peña-Rosas and Luz Maria De-Regil for their
foods or beverages can have a positive impact on Hb levels and
contribution to the design of this review.
reduce the risk of anaemia in infants, preschool and school-aged
children, pregnant women, and mixed populations. Furthermore, In addition, we thank Cochrane Developmental, Psychosocial and
there was no evidence of a difference in any adverse side effect Learning Problems for their support in the preparation of this
(e.g. diarrhoea, constipation, or vomiting) of the intervention, overview of reviews.
regardless of the types of trial participants or their ages.
We also thank Windy MV Wariki (WW) from the Faculty of Medicine,
We highlighted nutrition-specific interventions for apparently Sam Ratulangi University, Manado, Indonesia, for initial help in
healthy populations in this overview review. However, nutritional screening and data extraction.
anaemia accounts only for a portion of all anaemia cases and
multiple factors - nutritional and non-nutritional - can cause
(Review)
Informed decisions.
The CRG Editorial Team are grateful to the following reviewers of Nutrition, University of California, Davis; Denish Moorthy,
for their time and comments: Reina Engle-Stone, Department Senior Technical Advisor, USAID Advancing Nutrition; and Emma
Sydenham.
(Review)
Informed decisions.
REFERENCES
References to included reviews Systematic Reviews 2015, Issue 2. Art. No: CD007079. [DOI:
10.1002/14651858.CD007079.pub3] [PMID: 25922862]
Aaron 2015
Aaron GJ, Dror DK, Yang Z. Multiple-micronutrient fortified Casgrain 2012
non-dairy beverage interventions reduce the risk of anemia Casgrain A, Collings R, Harvey LJ, Hooper L, Fairweather-
and iron deficiency in school-aged children in low-middle Tait SJ. Effect of iron intake on iron status: a systematic review
income countries: a systematic review and meta-analysis (i- and meta-analysis of randomized controlled trials. American
iv). Nutrients 2015;7(5):3847-68. [DOI: 10.3390/nu7053847] Journal of Clinical Nutrition 2012;96(4):768-80. [DOI: 10.3945/
[PMC4446783] [PMID: 26007336] ajcn.112.040626] [PMID: 22932280]
Abdullah 2013 Daru 2016
Abdullah K, Kendzerska T, Shah P, Uleryk E, Parkin PC. Efficacy Daru J, Cooper NA, Khan KS. Systematic review of randomized
of oral iron therapy in improving the developmental outcome trials of the effect of iron supplementation on iron stores and
of pre-school children with non-anaemic iron deficiency: a oxygen carrying capacity in pregnancy. Acta Obstetricia et
systematic review. Public Health Nutrition 2013;16(8):1497-506. Gynecologica Scandinavica 2016;95(3):270-9. [DOI: 10.1111/
[DOI: 10.1017/S1368980012003709] [PMID: 22894941] aogs.12812] [PMID: 26509354]
Abe 2016 Das 2013a
Abe SK, Balogun OO, Ota E, Takahashi K, Mori R. Das JK, Kumar R, Salam RA, Bhutta ZA. Systematic review of
Supplementation with multiple micronutrients for zinc fortification trials. Annals of Nutrition & Metabolism 2013;62
breastfeeding women for improving outcomes for the mother Suppl 1:44-56. [DOI: 10.1159/000348262] [PMID: 23689112]
and baby. Cochrane Database of Systematic Reviews 2016, Issue
2. Art. No: CD010647. [DOI: 10.1002/14651858.CD010647.pub2] Das 2018
[PMID: 2688790] Das JK, Hoodbhoy Z, Salam RA, Bhutta AZ, Valenzuela-
Rubio NG, Weise Prinzo Z, et al. Lipid-based nutrient
Abu Hashim 2017
supplements for maternal, birth, and infant developmental
Abu Hashim H, Foda O, Ghayaty E. Lactoferrin or ferrous salts outcomes. Cochrane Database of Systematic Reviews 2018, Issue
for iron deficiency anemia in pregnancy: a meta-analysis of 8. Art. No: CD012610. [DOI: 10.1002/14651858.CD012610.pub2]
randomized trials. European Journal of Obstetrics, Gynecology,
and Reproductive Biology 2017;219:45-52. [DOI: 10.1016/ Das 2019a
j.ejogrb.2017.10.003] [PMID: 29059584] Das JK, Salam RA, Hadi YB, Sadiq Sheikh S, Bhutta AZ, Weise
Prinzo Z, et al. Preventive lipid-based nutrient supplements
Arabi 2020
given with complementary foods to infants and young children
Arabi SM, Ranjbar G, Bahrami LS, Vafa M, Norouzy A. The effect 6 to 23 months of age for health, nutrition, and developmental
of vitamin D supplementation on hemoglobin concentration: outcomes. Cochrane Database of Systematic Reviews 2019, Issue
a systematic review and meta-analysis. Nutrition Journal 5. Art. No: CD012611. [DOI: 10.1002/14651858.CD012611.pub3]
2020;19(1):11. [PMC6497129] [PMID: 31046132]
Basutkar 2019 Das 2019b
Basutkar RS, Tsundue T, Siva H, Rose A, Sivasankaran P. Vitamin Das JK, Salam RA, Mahmood SB, Moin A, Kumar R, Mukhtar K,
D supplementation in patients with iron deficiency anaemia: et al. Food fortification with multiple micronutrients: impact
a systematic review and a meta-analysis. Systematic Reviews on health outcomes in general population. Cochrane Database
in Pharmacy 2019;10(1):1-10. [DOI: 10.5530/srp.2019.1.1] of Systematic Reviews 2019, Issue 12. Art. No: CD011400. [DOI:
[www.sysrevpharm.org/fulltext/196-1568986036.pdf? 10.1002/14651858.CD011400.pub2] [PMC6917586] [PMID:
1614009224] 31849042]
Bhutta 2012 Dekker 2010
Bhutta ZA, Imdad A, Ramakrishnan U, Martorell R. Is it time to Dekker LH, Villamor E. Zinc supplementation in children is
replace iron folate supplements in pregnancy with multiple not associated with decreases in hemoglobin concentrations.
micronutrients? Paediatric and Perinatal Epidemiology 2012;26 Journal of Nutrition 2010;140(5):1035-40. [DOI: 10.3945/
Suppl 1:27-35. [DOI: 10.1111/j.1365-3016.2012.01313.x] [PMID: jn.109.119305] [PMID: 20335624]
22742600]
De-Regil 2011
Buppasiri 2015
De-Regil LM, Jefferds ME, Sylvetsky AC, Dowswell T. Intermittent
Buppasiri P, Lumbiganon P, Thinkhamrop J, Ngamjarus C, iron supplementation for improving nutrition and development
Laopaiboon M, Medley N. Calcium supplementation (other in children under 12 years of age. Cochrane Database of
than for preventing or treating hypertension) for improving Systematic Reviews 2011, Issue 12. Art. No: CD009085. [DOI:
pregnancy and infant outcomes. Cochrane Database of 10.1002/14651858.CD009085.pub2] [PMC4547491] [PMID:
22161444]
(Review)
Informed decisions.
De-Regil 2015 10.1002/14651858.CD010187.pub2] [PMC6517107] [PMID:

De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco- 30577080]
Solon P. Effects and safety of periconceptional oral folate
Geerligs 2003
supplementation for preventing birth defects. Cochrane
Database of Systematic Reviews 2015, Issue 12. Art. No: Geerligs PD, Brabin BJ, Omari AA. Food prepared in iron cooking
CD007950. [DOI: 10.1002/14651858.CD007950.pub3] [PMID: pots as an intervention for reducing iron deficiency anaemia in
26662928] developing countries: a systematic review. Journal of Human
Nutrition and Dietetics 2003;16(4):275-81. [DOI: 10.1046/
De-Regil 2017 j.1365-277x.2003.00447.x] [PMID: 12859709]
De-Regil LM, Jefferds ME, Pena-Rosas JP. Point-of-use
Gera 2007a
fortification of foods with micronutrient powders containing
iron in children of preschool and school-age. Cochrane Gera T, Sachdev HP, Nestel P, Sachdev SS. Effect of iron
Database of Systematic Reviews 2017, Issue 11. Art. No: supplementation on haemoglobin response in children:
CD009666. [DOI: 10.1002/14651858.CD009666.pub2] systematic review of randomised controlled trials. Journal of
[PMC6486284] [PMID: 29168569] Pediatric Gastroenterology and Nutrition 2007;44(4):468-86.
[DOI: 10.1097/01.mpg.0000243440.85452.38] [PMID: 17414146]
Dewey 2009
Gera 2009
Dewey KG, Yang Z, Boy E. Systematic review and meta-
analysis of home fortification of complementary foods. Gera T, Sachdev HP, Nestel P. Effect of combining multiple
Maternal & Child Nutrition 2009;5(4):283-321. [DOI: 10.1111/ micronutrients with iron supplementation on Hb response in
j.1740-8709.2009.00190.x] children: systematic review of randomized controlled trials.
Public Health Nutrition 2009;12(6):756-73. [DOI: 10.1017/
Eichler 2012 S1368980008003145] [PMID: 18671894]
Eichler K, Wieser S, Rüthemann I, Brügger U. Effects of
Gera 2012
micronutrient fortified milk and cereal food for infants and
children: a systematic review. BMC Public Health 2012;12:506. Gera T, Sachdev HS, Boy E. Effect of iron-fortified foods on
[DOI: 10.1186/1471-2458-12-506] [PMC3444335] [PMID: hematologic and biological outcomes: systematic review of
22770558] randomized controlled trials. American Journal of Clinical
Nutrition 2012;96(2):309-24. [DOI: 10.3945/ajcn.111.031500]
Eichler 2019 [PMID: 22760566]
Eichler K, Hess S, Twerenbold C, Sabatier M, Meier F, Wieser S.
Govindappagari 2019
Health effects of micronutrient fortified dairy products and
cereal food for children and adolescents: A systematic review. Govindappagari S, Burwick RM. Treatment of iron deficiency
PloS One 2019;14(1):e0210899. [PMID: 30673769] anemia in pregnancy with intravenous versus oral iron:
systematic review and meta-analysis. American Journal of
Fernández-Gaxiola 2019 Perinatology 2019;36(4):366-76. [PMID: 30121943]
Fernández-Gaxiola AC, De-Regil LM. Intermittent iron
Haider 2011
supplementation for reducing anaemia and its associated
impairments in adolescent and adult menstruating women. Haider BA, Yakoob MY, Bhutta ZA. Effect of multiple
Cochrane Database of Systematic Reviews 2019, Issue 1. Art. micronutrient supplementation during pregnancy on maternal
No: CD009218. [DOI: 10.1002/14651858.CD009218.pub3] and birth outcomes. BMC Public Health 2011;11 Suppl 3:S19.
[PMC6360921] [PMID: 30699468] [DOI: 10.1186/1471-2458-11-S3-S19] [PMC3231892] [PMID:
21501436]
Field 2020
Haider 2013
Field MS, Mithra P, Estevez D, Pena-Rosas JP. Wheat
flour fortification with iron for reducing anaemia and Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW.
improving iron status in populations. Cochrane Database of Anaemia, prenatal iron use, and risk of adverse pregnancy
Systematic Reviews 2020, Issue 7. Art. No: CD011302. [DOI: outcomes: systematic review and meta-analysis. BMJ
10.1002/14651858.CD011302.pub2] [PMID: 32677706] 2013;346:f3443. [DOI: 10.1136/bmj.f3443] [PMC3689887] [PMID:
23794316]
Finkelstein 2019
Hess 2016
Finkelstein JL, Fothergill A, Hackl LS, Haas JD, Mehta S. Iron
biofortification interventions to improve iron status and Hess S, Tecklenburg L, Eichler K. Micronutrient fortified
functional outcomes. Proceedings of the Nutrition Society condiments and noodles to reduce anemia in children and
2019;78(2):197-207. [PMID: 30698117] adults-a literature review and meta-analysis. Nutrients
2016;8(2):88. [DOI: 10.3390/nu8020088] [PMC4772051] [PMID:
Garcia-Casal 2018 26891319]
Garcia-Casal MN, Peña-Rosas JP, De-Regil LM, Gwirtz JA,
Houston 2018
Pasricha SR. Fortification of maize flour with iron for controlling
anaemia and iron deficiency in populations. Cochrane Database Houston BL, Hurrie D, Graham J, Perija B, Rimmer E, Rabbani R,
of Systematic Reviews 2018, Issue 12. Art. No: CD010187. [DOI: et al. Efficacy of iron supplementation on fatigue and
(Review)
Informed decisions.
physical capacity in non-anaemic iron-deficient adults: a and health in menstruating women. Cochrane Database of
systematic review of randomised controlled trials. BMJ Open Systematic Reviews 2016, Issue 4. Art. No: CD009747. [DOI:
2018;8(4):e019240. [DOI: 10.1136/bmjopen-2017-019240] 10.1002/14651858.CD009747.pub2] [PMID: 27087396]
[PMC5892776] [PMID: 29626044]
Matsuyama 2017
Huo 2015 Matsuyama M, Harb T, David M, Davies PS, Hill RJ. Effect
Huo JS, Yin JY, Sun J, Huang J, Lu ZX, Regina MP, et al. Effect of fortified milk on growth and nutritional status in
of NaFeEDTA-fortified soy sauce on anemia prevalence in young children: a systematic review and meta-analysis.
China: a systematic review and meta-analysis of randomized Public Health Nutrition 2017;20(7):1214-25. [DOI: 10.1017/
controlled trials. Biomedical and Environmental Sciences S1368980016003189] [PMID: 27938461]
2015;28(11):788-98. [DOI: 10.3967/bes2015.110] [PMID:
26695357] Mayo-Wilson 2014a
Mayo-Wilson E, Junior JA, Imdad A, Dean S, Chan XH, Chan ES,
Imdad 2012 et al. Zinc supplementation for preventing mortality, morbidity,
Imdad A, Bhutta ZA. Routine iron/folate supplementation and growth failure in children aged 6 months to 12 years of age.
during pregnancy: effect on maternal anaemia and birth Cochrane Database of Systematic Reviews 2014, Issue 5. Art.
outcomes. Paediatric and Perinatal Epidemiology 2012;26 No: CD009384. [DOI: 10.1002/14651858.CD009384.pub2] [PMID:
Suppl 1:168-77. [DOI: 10.1111/j.1365-3016.2012.01312.X] [PMID: 24826920]
22742609]
McCauley 2015
Keats 2019 McCauley ME, Van den Broek N, Dou L, Othman M. Vitamin A
Keats EC, Haider BA, Tam E, Bhutta ZA. Multiple-micronutrient supplementation during pregnancy for maternal and newborn
supplementation for women during pregnancy. Cochrane outcomes. Cochrane Database of Systematic Reviews 2015, Issue
Database of Systematic Reviews 2019, Issue 3. Art. No: 10. Art. No: CD008666. [DOI: 10.1002/14651858.CD008666.pub3]
CD004905. [DOI: 10.1002/14651858.CD004905.pub6] [PMC7173731] [PMID: 26503498]
[PMC6418471] [PMID: 30873598]
Neuberger 2016
Kristjansson 2015 Neuberger A, Okebe J, Yahav D, Paul M. Oral iron supplements
Kristjansson E, Francis DK, Liberato S, Benkhalti Jandu M, for children in malaria-endemic areas. Cochrane Database
Welch V, Batal M, et al. Food supplementation for improving of Systematic Reviews 2016, Issue 2. Art. No: CD006589. [DOI:
the physical and psychosocial health of socio-economically 10.1002/14651858.CD006589]
disadvantaged children aged three months to five years.
Cochrane Database of Systematic Reviews 2015, Issue 3. Art. Pasricha 2013
No: CD009924. [DOI: 10.1002/14651858.CD009924.pub2] Pasricha SR, Hayes E, Kalumba K, Biggs BA. Effect of daily iron
[PMC6885042] [PMID: 25739460] supplementation on health in children aged 4-23 months: a
systematic review and meta-analysis of randomised controlled
Lassi 2013 trials. Lancet. Global Health 2013;1(2):e77-86. [DOI: 10.1016/
Lassi ZS, Salam RA, Haider BA, Bhutta ZA. Folic acid S2214-109X(13)70046-9] [PMID: 25104162]
supplementation during pregnancy for maternal
health and pregnancy outcomes. Cochrane Database of Peña-Rosas 2015a
Systematic Reviews 2013, Issue 3. Art. No: CD006896. [DOI: Peña-Rosas JP, De-Regil LM, Gomez Malave H, Flores-
10.1002/14651858.CD006896.pub2] [PMID: 23543547] Urrutia MC, Dowswell T. Intermittent oral iron supplementation
during pregnancy. Cochrane Database of Systematic
Lassi 2020 Reviews 2015, Issue 10. Art. No: CD009997. [DOI:
Lassi ZS, Kedzior SG, Tariq W, Jadoon Y, Das JK, Bhutta ZA. 10.1002/14651858.CD009997.pub2] [PMC7092533] [PMID:
Effects of preconception care and periconception interventions 26482110]
on maternal nutritional status and birth outcomes in low-
and middle-income countries: a systematic review. Nutrients Peña-Rosas 2015b
2020;12(3):606. [PMID: 32110886] Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T.
Daily oral iron supplementation during pregnancy. Cochrane
Low 2013 Database of Systematic Reviews 2015, Issue 7. Art. No:
Low M, Farrell A, Biggs BA, Pasricha SR. Effects of daily iron CD004736. [DOI: 10.1002/14651858.CD004736.pub5] [PMID:
supplementation in primary-school-aged children: systematic 26198451]
review and meta-analysis of randomized controlled trials. CMAJ:
Canadian Medical Association Journal [Journal De L'Association Peña-Rosas 2019
Medicale Canadienne] 2013;185(17):E791-802. [DOI: 10.1503/ Peña-Rosas JP, Mithra P, Unnikrishnan B, Kumar N, De-Regil LM,
cmaj.130628] [PMC3832580] [PMID: 24130243] Nair NS, et al. Fortification of rice with vitamins and minerals
for addressing micronutrient malnutrition. Cochrane Database
Low 2016 of Systematic Reviews 2019, Issue 10. Art. No: CD009902. [DOI:
Low MS, Speedy J, Styles CE, De-Regil LM, Pasricha SR. Daily 10.1002/14651858.CD009902]
iron supplementation for improving anaemia, iron status
(Review)
Informed decisions.
Petry 2016b Salam 2016

Petry N, Olofin I, Boy E, Donahue Angel M, Rohner F. The effect Salam RA, Hooda M, Das JK, Arshad A, Lassi ZS, Middleton P, et
of low dose iron and zinc intake on child micronutrient status al. Interventions to improve adolescent nutrition: a systematic
and development during the first 1000 days of life: a systematic review and meta-analysis. Journal of Adolescent Health
review and meta-analysis. Nutrients 2016;8(12):773. [DOI: 2016;59(4S):S29-39. [DOI: 10.1016/j.jadohealth.2016.06.022]
10.3390/nu8120773] [PMC5188428] [PMID: 27916873] [PMC5026685] [PMID: 27664593]
Pratt 2015 Salam 2020

Pratt O. A review of the strategies used to reduce the prevalence Salam RA, Das JK, Irfan O, Ahmed W, Sheikh SS, Bhutta ZA.
of iron deficiency and iron deficiency anaemia in infants aged Effects of preventive nutrition interventions among adolescents
6-36 months. Nutrition Bulletin 2015;40(4):257-67. on health and nutritional status in low-and middle-income
countries: A systematic review. Campbell Systematic Reviews
Qassim 2018 2020;16(2):e1085.
Qassim A, Mol BW, Grivell RM, Grzeskowiak LE. Safety and
efficacy of intravenous iron polymaltose, iron sucrose and ferric Shapiro 2019
carboxymaltose in pregnancy: A systematic review. Australian & Shapiro MJ, Downs SM, Swartz HJ, Parker M, Quelhas D, Kreis K,
New Zealand Journal of Obstetrics & Gynaecology 2018;58:22-39. et al. A systematic review investigating the relation between
animal-source food consumption and stunting in children aged
Qassim 2019 6-60 months in low and middle-income countries. Advances in
Qassim A, Grivell RM, Henry A, Kidson-Gerber G, Shand A, Nutrition (Bethesda, Md.) 2019;10(5):827-47. [PMID: 31177279]
Grzeskowiak LE. Intravenous or oral iron for treating iron
deficiency anaemia during pregnancy: systematic review and Shi 2015
meta-analysis. Medical Journal of Australia 2019;211(8):367-73. Shi Q, Leng W, Wazir R, Li J, Yao Q, Mi C, et al. Intravenous
iron sucrose versus oral iron in the treatment of pregnancy
Radhika 2019 with iron deficiency anaemia: a systematic review.
Radhika AG, Sharma AK, Perumal V, Sinha A, Sriganesh V, Gynecologic and Obstetric Investigation 2015;80(3):170-8. [DOI:
Kulshreshtha V, et al. Parenteral versus oral iron for treatment of 10.1159/000376577] [PMID: 25824489]
iron deficiency anaemia during pregnancy and post-partum: a
systematic review. Journal of Obstetrics and Gynecology of India Silva Neto 2019
2019;69(1):13-24. Silva Neto LG, Santos Neto JE, Bueno NB, De Oliveira SL,
Ataide TD. Effects of iron supplementation versus dietary
Ramírez-Luzuriaga 2018 iron on the nutritional iron status: Systematic review with
Ramírez-Luzuriaga MJ, Larson LM, Mannar V, Martorell R. Impact meta-analysis of randomized controlled trials. Critical Reviews
of double-fortified salt with iron and iodine on hemoglobin, in Food Science and Nutrition 2019;59(16):2553-61. [DOI:
anemia, and iron deficiency anemia: a systematic review and 10.1080/10408398.2018.1459469] [PMID: 29611716]
meta-analysis. Advances in Nutrition 2018;9(3):207-18. [DOI:
10.1093/advances/nmy008] [PMC5952925] [PMID: 29767699] Smelt 2018
Smelt AF, Gussekloo J, Bermingham LW, Allen E, Dangour AD,
Reveiz 2011 Eussen SJ, et al. The effect of vitamin B12 and folic acid
Reveiz L, Gyte GM, Cuervo LG, Casasbuenas A. Treatments for supplementation on routine haematological parameters in
iron-deficiency anaemia in pregnancy. Cochrane Database of older people: an individual participant data meta-analysis.
Systematic Reviews 2011, Issue 10. Art. No: CD003094. [DOI: European Journal of Clinical Nutrition 2018;72(6):785-95. [DOI:
10.1002/14651858.CD003094.pub3] [PMID: 21975735] 10.1038/s41430-018-0118-x] [PMID: 29520083]
Rumbold 2015 Suchdev 2015

Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin Suchdev PS, Peña-Rosas JP, De-Regil LM. Multiple
C supplementation in pregnancy. Cochrane Database of micronutrient powders for home (point-of-use) fortification
Systematic Reviews 2015, Issue 9. Art. No: CD004072. [DOI: of foods in pregnant women. Cochrane Database of
10.1002/14651858.CD004072.pub3] [PMID: 26415762] Systematic Reviews 2015, Issue 6. Art. No: CD011158. [DOI:
10.1002/14651858.CD011158.pub2] [PMID: 26091836]
Sadighi 2019
Sadighi J, Nedjat S, Rostami R. Systematic review and Suchdev 2020
meta-analysis of the effect of iron-fortified flour on iron Suchdev PS, Jeerds ME, Ota E, da Silva Lopes K, De-Regil LM.
status of populations worldwide. Public Health Nutrition Home fortification of foods with multiple micronutrient
2019;22(18):3465-84. [PMID: 31486352] powders for health and nutrition in children under two years of
age. Cochrane Database of Systematic Reviews 2020, Issue 2. Art.
Salam 2013 No: CD008959. [DOI: 10.1002/14651858.CD008959.pub3] [PMID:
Salam RA, MacPhail C, Das JK, Bhutta ZA. Effectiveness of 32107773]
micronutrient powders (MNP) in women and children. BMC
Public Health 2013;13(Suppl 3):S22. [10.1186/1471-2458-13-S3-
S22] [24564207] [PMC3847468]
(Review)
Informed decisions.
Sultan 2019 and adults. Journal of Nutrition 2009;139(5):1022-30. [DOI:

Sultan P, Bampoe S, Shah R, Guo N, Estes J, Stave C, et al. 10.3945/jn.107.086199] [PMID: 19321586]
Oral vs intravenous iron therapy for postpartum anemia:
Ashman 2017
a systematic review and meta-analysis. American Journal
of Obstetrics and Gynecology 2019;221(1):19-29.e3. [PMID: Ashman AM, Brown LJ, Collins CE, Rollo ME, Rae KM. Factors
30578747] associated with effective nutrition interventions for pregnant
indigenous women: a systematic review. Journal of the Academy
Tablante 2019 of Nutrition and Dietetics 2017;117(8):1222-53.e2. [DOI: 10.1016/
Tablante EC, Pachón H, Guetterman HM, Finkelstein JL. j.jand.2017.03.012] [PMID: 28476322]
Fortification of wheat and maize flour with folic acid
Athe 2014
for population health outcomes. Cochrane Database of
Systematic Reviews 2019, Issue 7. Art. No: CD012150. [DOI: Athe R, Rao MVV, Nair KM. Impact of iron-fortified foods on Hb
10.1002/14651858.CD012150.pub2] [PMC6599881] [PMID: concentration in children (< 10 years): a systematic review and
31257574] meta-analysis of randomized controlled trials. Public Health
Nutrition 2014;17(3):579-86. [DOI: 10.1017/S1368980013000062]
Tay 2015 [PMID: 23388159]
Tay HS, Soiza RL. Systematic review and meta-analysis: what is
Athe 2020
the evidence for oral iron supplementation in treating anaemia
in elderly people? Drugs & Aging 2015;32(2):149-58. [DOI: Athe R, Dwivedi R, Pati S, Mazumder A, Banset U. Meta-analysis
10.1007/s40266-015-0241-5] [PMID: 25644019] approach on iron fortification and its effect on pregnancy and
its outcome through randomized, controlled trials. Journal of
Thompson 2013 Family Medicine and Primary Care 2020;9(2):513.
Thompson J, Biggs BA, Pasricha SR. Effects of daily iron
Bairwa 2017
supplementation in 2- to 5-year-old children: systematic
review and meta-analysis. Pediatrics 2013;131(4):739-53. [DOI: Bairwa M, Ahamed F, Sinha S, Yadav K, Kant S, Pandav CS.
10.1542/peds.2012-2256] [PMID: 23478873] Directly observed iron supplementation for control of
iron deficiency anemia. Indian Journal of Public Health
Thorne-Lyman 2012 2017;61(1):37.
Thorne-Lyman AL, Fawzi WW. Vitamin A and carotenoids
Best 2011
during pregnancy and maternal, neonatal and infant health
outcomes: a systematic review and meta-analysis. Paediatric Best C, Neufingerl N, Del Rosso JM, Transler C, Van den Briel T,
and Perinatal Epidemiology 2012;26(Suppl 1):36-54. [DOI: Osendarp S. Can multi-micronutrient food fortification improve
10.1111/j.1365-3016.2012.01284.x] [PMC3843354] [PMID: the micronutrient status, growth, health, and cognition
22742601] of schoolchildren? A systematic review. Nutrition Reviews
2011;69(4):186-204. [DOI: 10.1111/j.1753-4887.2011.00378.x]
Tolkien 2015 [PMID: 21457264]
Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous
Brown 2009
sulfate supplementation causes significant gastrointestinal
side-effects in adults: a systematic review and meta- Brown KH, Peerson JM, Baker SK, Hess SY. Preventive zinc
analysis. PloS One 2015;10(2):e0117383. [DOI: 10.1371/ supplementation among infants, preschoolers, and older
journal.pone.0117383] [PMC4336293] [PMID: 25700159] prepubertal children. Food and Nutrition Bulletin 2009;30(1
Suppl):S12-40. [DOI: 10.1177/15648265090301S103] [PMID:
Yadav 2019 19472600]
Yadav K, Goel AD, Yadav V, Upadhyay RP, Palepu S, Pandav CS.
Butler 2006
Meta-analysis of efficacy of iron and iodine fortified salt in
improving iron nutrition status. Indian Journal of Public Health Butler CC, Vidal-Alaball J, Cannings-John R, McCaddon A,
2019;63(1):58-64. [PMID: 30880739] Hood K, Papaioannou A, et al. Oral vitamin B12 versus
intramuscular vitamin B12 for vitamin B12 deficiency: a
systematic review of randomized controlled trials. Family
References to excluded reviews Practice 2006;23(3):279-85. [DOI: 10.1093/fampra/cml008]
[PMID: 16585128]
Agha 2014
Agha M, Agha RA, Sandall J. Interventions to reduce and prevent Câmara 2011
obesity in pre-conceptual and pregnant women: a systematic Câmara MC, Barreto AM, Medeiros AP, Lucena IF, Moura JV,
review and meta-analysis. PloS one 2014;9(5):e95132. [DOI: Oliveira TF. The use of games in health education in order
10.1371/journal.pone.0095132] [PMC4020754] [PMID: 24827704] to prevent iron deficiency anemia in infancy: the role of
the nurse - literature systematic review [A utilização da
Allen 2009
brincadeira na educação em saúde como prevenção da anemia
Allen LH, Peerson JM, Olney DK. Provision of multiple rather ferropriva na infância: atuação do enfermeiro – estudo de
than two or fewer micronutrients more effectively improves revisão integrativa]. Nursing Journal [Revista de Enfermagem]
growth and other outcomes in micronutrient-deficient children
(Review)
Informed decisions.
2011;5(5):1280-5. [DOI: 10.5205/reuol.1302-9310-2- Fishman 2000

LE.0505201127] Fishman SM, Christian P, West KP. The role of vitamins in the
prevention and control of anaemia. Public Health Nutrition
Cancelo-Hidalgo 2013
2000;3(2):125-50. [DOI: 10.1017/s1368980000000173] [PMID:
Cancelo-Hidalgo MJ, Castelo-Branco C, Palacios S, Haya- 10948381]
Palazuelos J, Ciria-Recasens M, Manasanch J, et al. Tolerability
of different oral iron supplements: a systematic review. Current Gavaravarapu 2017
Medical Research and Opinion 2013;29(4):291-303. [DOI: Gavaravarapu SM, Archana Konapur A, Saha S. Role of
10.1185/03007995.2012.761599] [PMID: 23252877] education and communication interventions in promoting
micronutrient status in India – what research in the last two
Chang 2018
decades informs. Journal of Communication in Healthcare
Chang CH, Tseng PT, Chen NY, Lin PC, Lin PY, Chang JP, et al. 2017;10(4):238-49. [DOI: 10.1080/17538068.2017.1338407]
Safety and tolerability of prescription omega-3 fatty acids: a
systematic review and meta-analysis of randomized controlled Gera 2007b
trials. Prostaglandins, Leukotrienes, and Essential Fatty Acids Gera T, Sachdev HP, Nestel P. Effect of iron supplementation on
2018;129:1-12. [DOI: 10.1016/j.plefa.2018.01.001] [PMID: physical performance in children and adolescents: systematic
29482765] review of randomized controlled trials. Indian Pediatrics
2007;44(1):15-24. [PMID: 17277426]
Da Cunha 2019
Da Cunha MS, Campos Hankins NA, Arruda SF. Effect of Ghanchi 2019
vitamin A supplementation on iron status in humans: a Ghanchi A, James PT, Cerami C. Guts, germs, and iron: a
systematic review and meta-analysis. Critical Reviews in systematic review on iron supplementation, iron fortification,
Food Science and Nutrition 2019;59(11):1767-81. [DOI: and diarrhea in children aged 4-59 months. Current
10.1080/10408398.2018.1427552] [PMID: 29336593] Developments in Nutrition 2019;3(3):nzz005. [PMID: 30891538]
Das 2013b Girard 2012a
Das JK, Salam RA, Kumar R, Bhutta ZA. Micronutrient Girard AW, Olude O. Nutrition education and counselling
fortification of food and its impact on woman and child health: provided during pregnancy: effects on maternal, neonatal
a systematic review. Systematic Reviews 2013;2:67. [DOI: and child health outcomes. Paediatric and Perinatal
10.1186/2046-4053-2-67] [PMC3765883] [PMID: 23971426] Epidemiology 2012;26 Suppl 1:191-204. [DOI: 10.1111/
j.1365-3016.2012.01278.x] [PMID: 22742611]
De Barros 2016
De Barros SF, Cardoso MA. Adherence to and acceptability Girard 2012b
of home fortification with vitamins and minerals in children Girard AW, Self JL, McAuliffe C, Olude O. The effects of
aged 6 to 23 months: a systematic review. BMC Public Health household food production strategies on the health and
2016;16:299. [DOI: 10.1186/s12889-016-2978-0] [PMC4823916] nutrition outcomes of women and young children: a systematic
[PMID: 27056182] review. Paediatric and Perinatal Epidemiology 2012;26 Suppl
1:205-22. [DOI: 10.1111/j.1365-3016.2012.01282.x] [PMID:
Dror 2012
22742612]
Dror DK, Allen LH. Interventions with vitamins B6, B12 and C
in pregnancy. Paediatric and Perinatal Epidemiology 2012;26 Guo 2015
Suppl 1:55-74. [DOI: 10.1111/j.1365-3016.2012.01277.x] [PMID: Guo XM, Liu H, Qian J. Daily iron supplementation on cognitive
22742602] performance in primary-school-aged children with and without
anemia: a meta-analysis. International Journal of Clinical and
Eaton 2019
Experimental Medicine 2015;8(9):16107-11. [PMC4659009]
Eaton JC, Rothpletz-Puglia P, Dreker MR, Iannotti L, Lutter C, [PMID: 26629120]
Kaganda J, et al. Effectiveness of provision of animal-source
foods for supporting optimal growth and development Gurusamy 2014
in children 6 to 59 months of age. Cochrane Database of Gurusamy KS, Nagendran M, Broadhurst JF, Anker SD,
Systematic Reviews 2019, Issue 2. Art. No: CD012818. [DOI: Richards T. Iron therapy in anaemic adults without
10.1002/14651858.CD012818.pub2] [PMC6380771] [PMID: chronic kidney disease. Cochrane Database of Systematic
30779870] Reviews 2014, Issue 12. Art. No: CD010640. [DOI:
10.1002/14651858.CD010640.pub2] [PMID: 25550190]
Falkingham 2010
Falkingham M, Abdelhamid A, Curtis P, Fairweather-Tait S, Haider 2018
Dye L, Hooper L. The effects of oral iron supplementation Haider LM, Schwingshackl L, Hoffmann G, Ekmekcioglu C.
on cognition in older children and adults: a systematic The effect of vegetarian diets on iron status in adults: a
review and meta-analysis. Nutrition Journal 2010;9:4. [DOI: systematic review and meta-analysis. Critical Reviews
10.1186/1475-2891-9-4] [PMC2831810] [PMID: 20100340] in Food Science and Nutrition 2018;58(8):1359-74. [DOI:
10.1080/10408398.2016.1259210] [PMID: 27880062]
(Review)
Informed decisions.
Iannotti 2006 2014;4(6):e004647. [DOI: 10.1136/bmjopen-2013-004647]

Iannotti LL, Tielsch JM, Black MM, Black RE. Iron [PMC4067863] [PMID: 24948745]
supplementation in early childhood: health benefits and risks.
McDonagh 2015a
American Journal of Clinical Nutrition 2006;84(6):1261-76. [DOI:
10.1093/ajcn/84.6.1261] [PMC3311916] [PMID: 17158406] McDonagh M, Blazina I, Dana T, Cantor A, Bougatsos C. Routine
iron supplementation and screening for iron deficiency anemia
Iglesias 2019 in children ages 6 to 24 months: a systematic review to update
Iglesias Vãzquez L, Valera E, Villalobos M, Tous M, Arija V. the US Preventive Services Task Force Recommendation; March
Prevalence of anemia in children from Latin America and 2015. Available at www.ncbi.nlm.nih.gov/books/NBK285660.
the Caribbean and effectiveness of nutritional interventions: [NBK285660] [PMID: 25905157]
systematic review and meta-analysis. Nutrients 2019;11(1):183.
McDonagh 2015b
[PMID: 30654514]
McDonagh M, Cantor A, Bougatsos C, Dana T, Blazina I. Routine
Iqbal 2019 iron supplementation and screening for iron deficiency anemia
Iqbal S, Ekmekcioglu C. Maternal and neonatal outcomes in pregnant women: a systematic review to update the US
related to iron supplementation or iron status: a summary Preventive Services Task Force Recommendation [Internet];
of meta-analyses. Journal of Maternal-Fetal & Neonatal March 2015. Available at www.ncbi.nlm.nih.gov/books/
Medicine: the official journal of the European Association of NBK285986. [NBK285986] [PMID: 25927136]
Perinatal Medicine, the Federation of Asia and Oceania Perinatal
McDonagh 2015c
Societies, the International Society of Perinatal Obstetricians
2019;32(9):1528-40. [PMID: 29207894] McDonagh MS, Blazina I, Dana T, Cantor A, Bougatsos C.
Screening and routine supplementation for iron deficiency
Jackson 2016 anemia: a systematic review. Pediatrics 2015;135(4):723-33.
Jackson J, Williams R, McEvoy M, MacDonald-Wicks L, [DOI: 10.1542/peds.2014-3979] [PMID: 25825534]
Patterson A. Is higher consumption of animal flesh foods
Michelazzo 2013
associated with better iron status among adults in developed
countries? A systematic review. Nutrients 2016;8(2):89. [DOI: Michelazzo FB, Oliveira JM, Stefanello J, Luzia LA, Rondó PHC.
10.3390/nu8020089] [PMC4772052] [PMID: 26891320] The influence of vitamin A supplementation on iron status.
Nutrients 2013;5(11):4399-413. [DOI: 10.3390/nu5114399]
Kong 2016 [MC3847738] [PMID: 24212089]
Kong K, Liu J, Tao Y. Limitations of studies on school-based
Middleton 2013
nutrition education interventions for obesity in China: a
systematic review and meta-analysis. Asia Pacific Journal Middleton P, Lassi Z, Tran TS, Bhutta ZA, Bubner T, Flenady V, et
of Clinical Nutrition 2016;25(3):589-601. [DOI: 10.6133/ al. Nutrition interventions and programs for reducing mortality
apjcn.092015.19] [PMID: 27440695] and morbidity in pregnant and lactating women and women
of reproductive age: a systematic review. Journal of Paediatrics
Lewkowitz 2019 and Child Health 2013;49:71. [DOI: 10.1111/jpc.12131]
Lewkowitz AK, Gupta A, Simon L, Sabol BA, Stoll C, Cooke E, et
Middleton 2018
al. Intravenous compared with oral iron for the treatment of
iron-deficiency anemia in pregnancy: a systematic review and Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF,
meta-analysis. Journal of Perinatology 2019;39(4):519-32. [DOI: Makrides M. Omega-3 fatty acid addition during pregnancy.
10.1038/s41372-019-0320-2] [PMID: 30692612] Cochrane Database of Systematic Reviews 2018, Issue 11. Art.
No: CD003402. [DOI: 10.1002/14651858.CD003402.pub3] [PMID:
Lohner 2012 30480773]
Lohner S, Fekete K, Berti C, Hermoso M, Cetin I, Koletzko B, et
Miles 2019
al. Effect of folate supplementation on folate status and health
outcomes in infants, children and adolescents: a systematic Miles LF, Litton E, Imberger G, Story D. Intravenous iron therapy
review. International Journal of Food Sciences and Nutrition for non-anaemic, iron-deficient adults. Cochrane Database of
2012;63(8):1014-20. [DOI: 10.3109/09637486.2012.683779] Systematic Reviews 2019, Issue 12. Art. No: CD013084. [DOI:
[PMID: 22574624] 10.1002/14651858.CD013084.pub2] [PMID: 31860749]
Martínez 2020 Milne 2009

Martínez Francés A, Leal Martínez-Bujanda J. Efficacy and Milne AC, Potter J, Vivanti A, Avenell A. Protein and energy
tolerability of oral iron protein succinylate: a systematic review supplementation in elderly people at risk from malnutrition.
of three decades of research. Current Medical Research and Cochrane Database of Systematic Reviews 2009, Issue 2. Art.
Opinion 2020;36(4):613-23. [PMID: 31944128] No: CD003288. [DOI: 10.1002/14651858.CD003288.pub3]
[PMC7144819] [PMID: 19370584]
Mayo-Wilson 2014b
Mirmiran 2012
Mayo-Wilson E, Imdad A, Junior J, Dean S, Bhutta ZA. Preventive
zinc supplementation for children, and the effect of additional Mirmiran P, Golzarand M, Serra-Majem L, Azizi F. Iron, iodine
iron: a systematic review and meta-analysis. BMJ Open and vitamin a in the middle East; a systematic review of
(Review)
Informed decisions.
deficiency and food fortification. Iranian Journal of Public Shao 2019

Health 2012;41(8):8-19. [PMC3469033] [PMID: 23113219] Shao Y, Luo W, Xu H, Zhang L, Guo Q. The efficacy of ferumoxytol
for iron deficiency anemia: a meta-analysis of randomized
Oddo 2019
controlled trials. Acta Haematologica 2019;142(3):125-31.
Oddo VM, Roshita A, Rah JH. Potential interventions targeting [PMID: 31434073]
adolescent nutrition in Indonesia: a literature review. Public
Health Nutrition 2019;22(1):15-27. [PMID: 30348243] Smith 2017
Smith ER, Shankar AH, Wu LS, Aboud S, Adu-Afarwuah S, Ali H,
Oh 2020
et al. Modifiers of the effect of maternal multiple micronutrient
Oh C, Keats EC, Bhutta ZA. Vitamin and mineral supplementation on stillbirth, birth outcomes, and infant
supplementation during pregnancy on maternal, birth, child mortality: a meta-analysis of individual patient data from 17
health and development outcomes in low- and middle-income randomised trials in low-income and middle-income countries.
countries: a systematic review and meta-analysis. Nutrients Lancet. Global health 2017;5(11):e1090-100. [DOI: 10.1016/
2020;12(2):491. [PMID: 32075071] S2214-109X(17)30371-6] [PMID: 29025632]
Oliveira 2016 Sun 2018
Oliveira JM, Allert R, East CE. Vitamin A supplementation Sun J, Zhang L, Cui J, Li S, Lu H, Zhang Y, et al. Effect of dietary
for postpartum women. Cochrane Database of Systematic intervention treatment on children with iron deficiency
Reviews 2016, Issue 3. Art. No: CD005944. [DOI: anemia in China: a meta-analysis. Lipids in Health and
10.1002/14651858.CD005944.pub3] [PMID: 27012320] Disease 2018;17(1):108. [DOI: 10.1186/s12944-018-0749-x]
[PMC5944174] [PMID: 29747646]
Osungbade 2012
Osungbade KO, Oladunjoye AO. Preventive treatments of iron Szajewska 2010
deficiency anaemia in pregnancy: a review of their effectiveness Szajewska H, Ruszczynski M, Chmielewska A. Effects of iron
and implications for health system strengthening. Journal of supplementation in nonanemic pregnant women, infants, and
Pregnancy 2012;2012(454601):1-7. [DOI: 10.1155/2012/454601] young children on the mental performance and psychomotor
[PMC3400371] [PMID: 22848829] development of children: a systematic review of randomized
controlled trials. American Journal of Clinical Nutrition
Pachón 2015
2010;91(6):1684-90. [DOI: 10.3945/ajcn.2010.29191] [PMID:
Pachón H, Spohrer R, Mei Z, Serdula MK. Evidence of 20410098]
the effectiveness of flour fortification programs on iron
status and anemia: a systematic review. Nutrition Reviews Tam 2020
2015;73(11):780-95. [DOI: 10.1093/nutrit/nuv037] [PMID: Tam E, Keats EC, Rind F, Das JK, Bhutta ZA. Micronutrient
26433017] Supplementation and Fortification Interventions on Health and
Development Outcomes among Children Under-Five in Low-
Pasricha 2009
and Middle-Income Countries: A Systematic Review and Meta-
Pasricha S, Shet A, Sachdev HP, Shet AS. Risks of routine iron Analysis. Nutrients 2020;12(2):289. [PMID: 31973225]
and folic acid supplementation for young children. Indian
Pediatrics 2009;46(10):857-66. [PMID: 19887691] Vonderheid 2019
Vonderheid SC, Tussing-Humphreys L, Park C, Pauls H,
Pasricha 2014
OjiNjideka Hemphill N, LaBomascus B, et al. A systematic
Pasricha SR, Low M, Thompson J, Farrell A, De-Regil LM. review and meta-analysis on the effects of probiotic species
Iron supplementation benefits physical performance in on iron absorption and iron status. Nutrients 2019;11(12):2938.
women of reproductive age: a systematic review and meta- [PMID: 31816981]
analysis. Journal of Nutrition 2014;144(6):906-14. [DOI: 10.3945/
jn.113.189589] [PMID: 24717371] Xu 2019
Xu J, Li Y, Huo J, Sun J, Huang J. Supplementing fortified
Sachdev 2005
soybean powder reduced anemia in infants and young children
Sachdev HP, Gera T, Nestel P. Effect of iron supplementation aged 6-24 months. Nutrition Research 2019;63:21-33. [PMID:
on mental and motor development in children: systematic 30824394]
review of randomised controlled trials. Public Health Nutrition
2005;8(2):117-32. [DOI: 10.1079/phn2004677] [PMID: 15877905] Yadav 2020
Yadav K, Arjun MC, Jacob OM, Kant S, Ahamed F, Ramaswamy G.
Sguassero 2012
Comparison of different doses of daily iron supplementation for
Sguassero Y, De Onis M, Bonotti AM, Carroli G. Community- anemia prophylaxis in pregnancy: A systematic review. Journal
based supplementary feeding for promoting the growth of of Family Medicine and Primary Care 2020;9(3):1308-16. [PMID:
children under five years of age in low and middle income 32509609]
countries. Cochrane Database of Systematic Reviews 2012, Issue
6. Art. No: CD005039. [DOI: 10.1002/14651858.CD005039.pub3]
[PMID: 22696347]
(Review)
Informed decisions.
Additional references Baltussen 2004

Adish 1999 Baltussen R, Knai C, Sharan M. Iron fortification and iron
supplementation are cost-effective interventions to reduce iron
Adish AA, Esrey SA, Gyorkos TW, Jean-Baptiste J, Rojhani A.
deficiency in four subregions of the world. Journal of Nutrition
Effect of consumption of food cooked in iron pots on iron
2004;134(10):2678-84. [DOI: 10.1093/jn/134.10.2678] [PMID:
status and growth of young children: a randomised trial. Lancet
15465766]
1999;353(9154):712-6. [DOI: 10.1016/S0140-6736(98)04450-X]
[PMID: 10073514] Beck 2014
Alaofè 2009 Beck KL, Conlon CA, Kruger R, Coad J. Dietary determinants
of and possible solutions to iron deficiency for young
Alaofè H, Zee J, Dossa R, O'Brien HT. Education and improved
women living in industrialized countries: a review. Nutrients
iron intakes for treatment of mild iron-deficiency anemia in
2014;6(9):3747-76. [DOI: 10.3390/nu6093747] [PMC4179187]
adolescent girls in southern Benin. Food and Nutrition Bulletin
[PMID: 25244367]
2009;30(1):24-36. [DOI: 10.1177/156482650903000103] [PMID:
19445257] Beutler 2003
Allen 2000 Beutler E, Hoffbrand AV, Cook JD. Iron deficiency and
overload. Hematology 2003;2003:40-61. [DOI: 10.1182/
Allen LH. Anemia and iron deficiency: effects on pregnancy
asheducation-2003.1.40] [PMID: 14633776]
outcome. American Journal of Clinical Nutrition 2000;71(Suppl
5):1280S-4S. [DOI: 10.1093/ajcn/71.5.1280s] [PMID: 10799402] Brabin 2001a
Allen 2008 Brabin BJ, Hakimi M, Pelletier D. An analysis of anemia and
pregnancy-related maternal mortality. Journal of Nutrition
Allen LH. To what extent can food-based approaches improve
2001;131(2S-2):604S-14S; discussion 614S-5S. [DOI: 10.1093/
micronutrient status? Asia Pacific Journal of Clinical Nutrition
jn/131.2.604S] [PMID: 11160593]
2008;17 Suppl 1:103-5. [PMID: 18296313]
Brabin 2001b
Alves 2019
Brabin BJ, Premji Z, Verhoeff F. An analysis of anemia and
Alves C, Saleh A, Alaofè H. Iron-containing cookware for the
child mortality. Journal of Nutrition 2001;131(2S-2):636S-45S;
reduction of iron deficiency anemia among children and
discussion 646S-8S. [DOI: 10.1093/jn/131.2.636S] [PMID:
females of reproductive age in low- and middle-income
11160595]
countries: a systematic review. PloS one 2019;14(9):e0221094.
[DOI: 10.1371/journal.pone.0221094] [PMC6719866] [PMID: Butwick 2017
31479458]
Butwick A, Bampoe S, Sultan P. A systematic review of
An 2020 the efficacy of oral vs intravenous iron therapy for the
treatment of postpartum anemia. PROSPERO 2017. [Available
An P, Liu Y, Xu T, Zhang X, Min J, Wang F. Effects of probiotics/
from: www.crd.york.ac.uk/prospero/display_ record.php?
prebiotics/synbiotics supplementation on iron status and
ID=CRD42017080234] [CRD42017080234]
anemia. PROSPERO 2020. [Available from www.crd.york.ac.uk/
prospero/display_ record.php?ID=CRD42020182785] Camaschella 2015
[CRD42020182785]
Camaschella C. Iron-deficiency anemia. New England Journal of
Andersen 2016 Medicine 2015;372(19):1832-43. [DOI: 10.1056/NEJMra1401038]
[PMID: 25946282]
Andersen C, Noor R, Fawzi W, Mozaffarian D. Child iron
supplementation or fortification for anemia, growth, infection, CASP 2013
and developmental outcomes: a systematic review and meta-
Critical Appraisal Skills Programme (CASP). CASP Checklists.
analysis of randomized trials. PROSPERO 2016. [Available
casp-uk.net/casp-tools-checklists (accessed 31 July 2015).
from www.crd.york.ac.uk/prospero/display_ record.php?
ID=CRD42016039948] [CRD42016039948] Cavalli-Sforza 2005
Armstrong 2017 Cavalli-Sforza T, Berger J, Smitasiri S, Viteri F. Weekly iron-folic
acid supplementation of women of reproductive age: impact
Armstrong GR, Dewey CE, Summerlee AJ. Iron release from
overview, lessons learned, expansion plans, and contributions
the Lucky Iron Fish®: safety considerations. Asia Pacific
toward achievement of the millennium development goals.
Journal of Clinical Nutrition 2017;26(1):148-55. [DOI: 10.6133/
Nutrition Reviews 2005;63(12 Pt 2):S152-8. [PMID: 16466092]
apjcn.102015.14] [PMID: 28049274]
CDR 2009
Bager 2014
Centre for Reviews and Dissemination (CDR). Systematic
Bager P. Fatigue and acute/chronic anaemia. Danish Medical
reviews. CRD’s guidance for undertaking reviews in health
Journal 2014;61(4):B4824. [PMID: 24814598]
care; 2009. Available at www.york.ac.uk/media/crd/
Systematic_Reviews.pdf.
(Review)
Informed decisions.
Charles 2011 card/en/c/5aacbe39-068f-513b-b17d-1d92959654ea. [ISBN

Charles CV, Summerlee AJ, Dewey CE. Iron content of 9789251067499]
Cambodian foods when prepared in cooking pots containing
Fortin 2018
an iron ingot. Tropical Medicine & International Health
2011;16(12):1518-24. [DOI: 10.1111/j.1365-3156.2011.02878.x] Fortin PM, Hopewell S, Estcourt LJ. Red blood cell transfusion
[PMID: 21906213] to treat or prevent complications in sickle cell disease:
an overview of Cochrane Reviews. Cochrane Database of
Da Rocha 2017 Systematic Reviews 2018, Issue 8. Art. No: CD012082. [DOI:
Da Rocha TA, Silva Neto LG, Bezerra Bueno N, Dos Santos 10.1002/14651858.CD012082.pub2] [PMC6513377] [PMID:
Neto JE, De Oliveira SL. The effects of iron supplementation 30067867]
versus dietary iron on iron reserves in children: a systematic
Gadhave 2020
review and meta-analysis. PROSPERO 2017. [Available
from: www.crd.york.ac.uk/prospero/display_ record.php? Gadhave S, Babu GR, Deepa R, Lobo E, Saldanha ND. Effect
ID=CRD42017075118] [CRD42017075118] of meal supplementation during the antenatal period on
the improvement in maternal and birth weight. PROSPERO
Dary 2002 2020. [Available from www.crd.york.ac.uk/prospero/display_
Dary O, Mora JO, International Vitamin A Consultative Group. record.php?ID=CRD42020175138] [CRD42020175138]
Food fortification to reduce vitamin A deficiency: International
GBDPC 2016
Vitamin A Consultative Group recommendations. Journal
of Nutrition 2002;132(Suppl 9):2927S-33S. [DOI: 10.1093/ Global Burden of Disease Pediatrics Collaboration, Kyu HH,
jn/132.9.2927S] [PMID: 12221271] Pinho C, Wagner JA, Brown JC, Bertozzi-Villa A, Charlson FJ, et
al. Global and national burden of diseases and injuries among
Da Silva Lopes 2017 children and adolescents between 1990 and 2013: findings
Da Silva Lopes K, Ota E, Shakya P, Dagvadorj A, Balogun OO, from the Global Burden of Disease 2013 Study. JAMA Pediatrics
Peña-Rosas JP, et al. Effects of nutrition interventions during 2016;170(3):267-87. [DOI: 10.1001/jamapediatrics.2015.4276]
pregnancy on low birth weight: an overview of systematic [PMC5076765] [PMID: 26810619]
reviews. BMJ Global Health 2017;2(3):e000389. [DOI: 10.1136/
Global Nutrition Report 2020
bmjgh-2017-000389] [PMC5623264] [PMID: 29018583]
Global Nutrition Report Team. 2020 Global Nutrition Report:
De Benoist 2008 Action on Equity to End Malnutrition. Bristol (UK): Development
De Benoist B. Conclusions of a WHO Technical Consultation on Initiatives, 2020. [Available at globalnutritionreport.org/
folate and vitamin B12 deficiencies. Food and Nutrition Bulletin reports/2020-global-nutrition-report/]
2008;29(Suppl 2):S238-44. [DOI: 10.1177/15648265080292S129]
Gordon 2021
[PMID: 18709899]
Gordon M, Sinopoulou V, Iheozor-Ejiofor Z, Iqbal T, Allen P,
Dubey 2019 Hoque S, et al. Interventions for treating iron deficiency
Dubey S, Sahay MR, Verma P, Pati S, Singh Kshatri J, Kanungo S. anaemia in inflammatory bowel disease. Cochrane Database
A systematic review and meta-analysis on the effect of food of Systematic Reviews 2021, Issue 1. Art. No: CD013529. [DOI:
fortification with micronutrients (iron/folic acid/vitamin B12, or 10.1002/14651858.CD013529.pub2] [PMC8092475 (available on
combination) on anemia among pregnant women. PROSPERO 2022-01-20)] [PMID: 33471939]
2019. [Available from www.crd.york.ac.uk/prospero/display_
Haider 2017
record.php?ID=CRD42019146388] [CRD42019146388]
Haider BA, Bhutta ZA. Multiple-micronutrient supplementation
EPOC 2019 for women during pregnancy. Cochrane Database of
Cochrane Effective Practice and Organisation of Systematic Reviews 2017, Issue 4. Art. No: CD004905. [DOI:
Care (EPOC). Suggested risk of bias criteria for EPOC 10.1002/14651858.CD004905.pub5] [PMID: 28407219]
reviews. epoc.cochrane.org/sites/epoc.cochrane.org/
Hansen 2020
files/public/uploads/Resources-for-authors2017/
suggested_risk_of_bias_criteria_for_epoc_reviews.pdf Hansen R, Schroll JB, Sejer EP, Holm C. Benefits and risks of
(accessed April 2019). daily oral iron supplementation in pregnancy in iron replete
non-anaemic women: a systematic review. PROSPERO 2020.
Faggion 2015 [Available from www.crd.york.ac.uk/prospero/display_
Faggion CM Jr. Critical appraisal of AMSTAR: challenges, record.php?ID=CRD42020186210] [CRD42020186210]
limitations, and potential solutions from the perspective of an
Hare 2018
assessor. BMC Medical Research Methodology 2015;15:63. [DOI:
10.1186/s12874-015-0062-6] [PMC4535290] [PMID: 26268372] Hare D, Braat S, Cardoso B, Morgan C, Szymlek-Gay E, Biggs BA.
Health outcomes of iron supplementation and/or food
FAO 2011 fortification in iron-replete children aged 4-24 months: a
Food and Agriculture Organization of the United Nations. systematic review and meta-analysis of randomised controlled
Guidelines for measuring household and individual dietary trials. PROSPERO 2018. [Available from www.crd.york.ac.uk/
diversity; 2011. Available at www.fao.org/publications/
(Review)
Informed decisions.
prospero/display_ record.php?ID=CRD42018093744] Jackson 2005

[CRD42018093744] Jackson N, Waters E, Guidelines for Systematic Reviews
in Health Promotion and Public Health Taskforce. Criteria
Heath 2002
for the systematic review of health promotion and public
Heath AL, Fairweather-Tait SJ. Clinical implications of changes health interventions. Health Promotion International
in the modern diet: iron intake, absorption and status. Best 2005;20(4):367-74. [DOI: 10.1093/heapro/dai022] [PMID:
Practice & Research. Clinical Haematology 2002;15(2):225-41. 16169885]
[PMID: 12401305]
Jadad 1996
Higgins 2011
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ,
Higgins JP, Altman DG, Sterne JA, editor(s). Chapter 8: Assessing Gavaghan DJ, et al. Assessing the quality of reports
risk of bias in included studies. In: Higgins JP, Green S, of randomized clinical trials: is blinding necessary?
editor(s). Cochrane Handbook for Systematic Reviews of Controlled Clinical Trials 1996;17(1):1-12. [DOI:
Interventions Version 5.1.0 (updated March 2011). The Cochrane 10.1016/0197-2456(95)00134-4] [8721797]
Collaboration, 2011. Available from training.cochrane.org/
handbook/archive/v5.1/. Jere 2020
Jere M, Amenyah S, McNulty H, Hoey L, Price R, Gairhre S.
Higgins 2021
The effects of B vitamins and/or iron on haematological
Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, parameters and nutrient biomarkers of anaemia in children
et al editor(s). Cochrane Handbook for Systematic Reviews of in low- and middle-income countries: a systematic review
Interventions Version 6.2 (updated February 2021). Cochrane, and meta-analysis of randomized controlled trials. PROPERO
2021. Available from training.cochrane.org/handbook. 2020. [Available from www.crd.york.ac.uk/prospero/display_
record.php?ID=CRD42020166563] [CRD42020166563]
Hombali 2019
Hombali AS, Solon JA, Venkatesh BT, Nair NS, Peña-Rosas JP. Kapur 2003
Fortification of staple foods with vitamin A for vitamin A Kapur D, Sharma S, Agarwal KN. Effectiveness of nutrition
deficiency. Cochrane Database of Systematic Reviews 2019, Issue education, iron supplementation or both on iron status
5. Art. No: CD010068. [DOI: 10.1002/14651858.CD010068.pub2] in children. Indian pediatrics 2003;40(12):1131-44. [PMID:
[PMC6509778] [PMID: 31074495] 14722364]
Horton 2003 Kassebaum 2014
Horton S, Ross J. The economics of iron deficiency. Food Policy Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N,
2003;28(1):51-75. [DOI: 10.1016/S0306-9192(02)00070-2] Lozano R, et al. A systematic analysis of global anemia burden
from 1990 to 2010. Blood 2014;123(5):615-24. [DOI: 10.1182/
Hultcrantz 2017
blood-2013-06-508325] [PMC3907750] [PMID: 24297872]
Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, et
al. The GRADE Working Group clarifies the construct of certainty Lönnerdal 2017
of evidence. Journal of Clinical Epidemiology 2017;87:4-13. [DOI: Lönnerdal B. Excess iron intake as a factor in growth, infections,
10.1016/j.jclinepi.2017.05.006] [PMC6542664] [PMID: 28529184] and development of infants and young children. American
Journal of Clinical Nutrition 2017;106(Suppl 6):1681S-7S. [DOI:
Hurrell 1999
10.3945/ajcn.117.156042] [PMC5701711] [PMID: 29070544]
Hurrell RF, Reddy M, Cook JD. Inhibition of non-haem iron
absorption in man by polyphenolic-containing beverages. Lopez 2016
British Journal of Nutrition 1999;81(4):289-95. [PMID: 10999016] Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron
deficiency anaemia. Lancet 2016;387(10021):907-16. [DOI:
Hurrell 2002
10.1016/S0140-6736(15)60865-0] [PMID: 26314490]
Hurrell RF. Fortification: overcoming technical and practical
barriers. Journal of Nutrition 2002;132(4 Suppl):806S-12S. [DOI: Lynch 2000
10.1093/jn/132.4.806S] [PMID: 11925486] Lynch SR. The effect of calcium on iron absorption.
Nutrition Research Reviews 2000;13(2):141-58. [DOI:
Hurrell 2010
10.1079/095442200108729043] [PMID: 19087437]
Hurrell R, Egli I. Iron bioavailability and dietary reference values.
American Journal of Clinical Nutrition 2010;91(5):1461S-7S. [DOI: Man 2021
10.3945/ajcn.2010.28674F] [PMID: 20200263] Man Y, Xu T, Adhikari B, Zhou C, Wang Y, Wang B. Iron
supplementation and iron-fortified foods: a review. Critical
Hurrell 2012
Reviews in Food Science and Nutrition 2021 Jan 28 [Epub
Hurrell RF. Influence of inflammatory disorders and infection ahead of print]. [DOI: 10.1080/10408398.2021.1876623] [PMID:
on iron absorption and efficacy of iron-fortified foods. Nestle 33506686]
Nutrition Institute Workshop Series 2012;70:107-16. [DOI:
10.1159/000337673] [PMC4353607] [PMID: 25762975]
(Review)
Informed decisions.
Mason 2013 PAHO 2003

Mason J, Martorell R, Saldanha L, Shrimpton R. Reduction of Pan American Health Organization (PAHO). Guiding Principles
anaemia. Lancet Global Health 2013;1(1):e4-6. [DOI: 10.1016/ for Complementary Feeding of the Breastfed Child. Washington
S2214-109X(13)70009-3] [PMID: 25103585] (DC): PAHO, 2003. [www.who.int/nutrition/publications/
guiding_ principles_ compfeeding_ breastfed.pdf]
Milman 2020
Milman NT. A review of nutrients and compounds, which Pasricha 2011
promote or inhibit intestinal iron absorption: making a platform Pasricha SR. Daily iron supplementation for improving
for dietary measures that can reduce iron uptake in patients anaemia and health in children. PROSPERO 2011. [Available
with genetic haemochromatosis. Journal of Nutrition and from www.crd.york.ac.uk/prospero/display_ record.php?
Metabolism 2020;2020:7373498. [DOI: 10.1155/2020/7373498] ID=CRD42011001208] [CRD42011001208]
[PMC7509542] [PMID: 33005455]
Petry 2016a
Moher 2009 Petry N, Olofin I, Hurrell RF, Boy E, Wirth JP, Moursi M, et al.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. The proportion of anemia associated with iron deficiency
Preferred reporting items for systematic reviews and in low, medium, and high human development index
meta-analyses: the PRISMA statement. PLoS Medicine countries: a systematic analysis of national surveys. Nutrients
2009;6(7):e1000097. [DOI: 10.1371/journal.pmed.1000097] 2016;8(11):E693. [DOI: 10.3390/nu8110693] [PMC5133080]
[PMC2707599] [PMID: 19621072] [PMID: 27827838]
Moore 2014 Prentice 2017

Moore JB, Heffernan A, Allcock D, Holmes M, Evans C. A Prentice AM, Mendoza YA, Pereira D, Cerami C, Wegmuller R,
systematic review and meta-analysis of the evidence for Constable A, et al. Dietary strategies for improving iron
the regulation of dietary iron bioavailability by vitamin C status: balancing safety and efficacy. Nutrition Reviews
and phytate, in the context of hepcidin, and subsequent 2017;75(1):49-60. [DOI: 10.1093/nutrit/nuw055] [PMC5155616]
effects on iron status. PROSPERO 2014. [Available from [PMID: 27974599]
www.crd.york.ac.uk/prospero/display_ record.php?
ID=CRD42014010453] [CRD42014010453] Prinsen 2002
Prinsen Geerligs P, Brabin B, Mkumbwa A, Broadhead R,
Morck 1983 Cuevas LE. Acceptability of the use of iron cooking pots to
Morck TA, Lynch SR, Cook JD. Inhibition of food iron reduce anaemia in developing countries. Public Health Nutrition
absorption by coffee. American Journal of Clinical Nutrition 2002;5(5):619-24. [DOI: 10.1079/PHN2002341] [PMID: 12372154]
1983;37(3):416-20. [DOI: 10.1093/ajcn/37.3.416] [PMID: 6402915]
Rahman 2019
Nandi 2016 Rahman RA, Idris IB. Systematic review of randomised
Nandi A, Ashok A, Kinra S, Behrman JR, Laxminarayan R. Early controlled trials for effectiveness of interventions for prevention
childhood nutrition is positively associated with adolescent of anaemia in pregnancy. PROSPERO 2019. [Available
educational outcomes: evidence from the Andhra Pradesh from www.crd.york.ac.uk/prospero/display_ record.php?
Child and Parents Study (APCAPS). Journal of Nutrition ID=CRD42020184283] [CRD42020184283]
2016;146(4):806-13. [DOI: 10.3945/jn.115.223198] [PMC4807645]
[PMID: 26962175] Rogozinska 2018
Rogozinska E, Daru J, Nicolaides M, Robinson S, Saborido CM,
NHLBI Zamora J, et al. Iron treatments (Fe) in reproductive age women
National Heart, Lung and Blood Institute (NHLBI). Study Quality with Iron Deficient Anaemia (FRIDA): a systematic review
Assessment Tools. Available at www.nhlbi.nih.gov/health- with network meta-analysis of randomised controlled trials.
topics/study-quality-assessment-tools. PROSPERO 2018. [Available from www.crd.york.ac.uk/prospero/
display_ record.php?ID=CRD42018100822] [CRD42018100822]
Nikooyeh 2018
Nikooyeh B, Neyestani TR. Nutritional impacts of home- Rosli 2019
fortification strategies in children younger than 5 year-old: Rosli RR, Noor NM. Iron polymaltose complex for iron
a systematic review and meta-analysis. PROSPERO 2018. deficiency anaemia in children. PROSPERO 2019. [Available
[Available from: https://www.crd.york.ac.uk/prospero/display_ from www.crd.york.ac.uk/prospero/display_ record.php?
record.php?ID=CRD42018109279] [CRD42018109279] ID=CRD42019145020] [CRD42019145020]
Paganini 2017 Ruel 2003

Paganini D, Zimmermann MB. The effects of iron fortification Ruel MT. Operationalizing dietary diversity: a review of
and supplementation on the gut microbiome and diarrhea measurement issues and research priorities. Journal of
in infants and children: a review. American Journal of Clinical Nutrition 2003;133(11 Suppl 2):3911S-26S. [DOI: 10.1093/
Nutrition 2017;106(Suppl 6):1688S-93S. [DOI: 10.3945/ jn/133.11.3911S] [MEDLINE: 14672290]
ajcn.117.156067] [PMC5701709] [PMID: 29070552]
(Review)
Informed decisions.
Ruel 2013 Deficiency Anemia. Washington (DC): ILSI Press, 1998. [ISBN
Ruel MT, Alderman H, Maternal and Child Nutrition Study Group. 1-57881-020-5] [motherchildnutrition.org/nutrition-protection-
Nutrition-sensitive interventions and programmes: how can promotion/pdf/mcn-guidelines-for-iron-supplementation.pdf]
they help to accelerate progress in improving maternal and
Stoltzfus 2004
child nutrition? Lancet 2013;382(9891):536-51. [DOI: 10.1016/
S0140-6736(13)60843-0] [PMID: 23746780] Stoltzfus RJ, Mullany L, Black RE. Iron deficiency anaemia.
In: Ezzati M, Lopez AD, Rodgers A, Murray CJL, editors(s).
Sharifirad 2011 Comparative Quantification of Health Risks: Global and
Sharifirad G, Golshiri P, Shahnazi H, Shakouri S, Hassanzadeh A. Regional Burden of Disease Attributable to Selected Major
PRECEDE educational model for controlling iron-deficiency Risk Factors. Vol. 1. Geneva (CH): World Health Organization,
anaemia in Talesh, Iran. Journal of the Pakistan Medical 2004:163–210. [ISBN 92 4 158031 3] [apps.who.int/iris/
Association 2011;61(9):862-5. [PMID: 22360024] bitstream/handle/10665/42792/9241580348_ eng_
Volume1.pdf?sequence=1]
Shea 2007a
Teucher 2004
Shea BJ, Bouter LM, Peterson J, Boers M, Andersson N, Ortiz Z,
et al. External validation of a measurement tool to assess Teucher B, Olivares M, Cori H. Enhancers of iron absorption:
systematic reviews (AMSTAR). PLoS One 2007;2(12):e1350. [DOI: ascorbic acid and other organic acids. International Journal
10.1371/journal.pone.0001350] [PMC2131785] [PMID: 18159233] for Vitamin and Nutrition Research 2004;74(6):403-19. [DOI:
10.1024/0300-9831.74.6.403] [PMID: 15743017]
Shea 2007b
Tsang 2015
Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N,
Hamel C, et al. Development of AMSTAR: a measurement Tsang B, Sandalinas F, De-Regil LM. Folate supplementation
tool to assess the methodological quality of systematic in women of reproductive age. Cochrane Database of
reviews. BMC Medical Research Methodology 2007;7:10. [DOI: Systematic Reviews 2015, Issue 6. Art. No: CD011766. [DOI:
10.1186/1471-2288-7-10] [PMC1810543] [PMID: 17302989] 10.1002/14651858.CD011766]
Shea 2009 UN 2015

Shea BJ, Hamel C, Wells GA, Bouter LM, Kristjansson E, United Nations. Transforming our world: the 2030 Agenda for
Grimshaw J, et al. AMSTAR is a reliable and valid measurement Sustainable Development. sustainabledevelopment.un.org/
tool to assess the methodological quality of systematic reviews. content/documents/21252030%20Agenda%20for
Journal of Clinical Epidemiology 2009;62(10):1013-20. [DOI: %20Sustainable%20Development%20web.pdf (accessed 25
10.1016/j.jclinepi.2008.10.009] [PMID: 19230606] June 2018).
Siegfried 2012 UNICEF 1999

Siegfried N, Irlam JH, Visser ME, Rollins NN. Micronutrient United Nations Children's Fund (UNICEF), World Health
supplementation in pregnant women with HIV infection. Organization (WHO), United Nations University (UNU).
Cochrane Database of Systematic Reviews 2012, Issue 3. Art. No: Composition of a multi-micronutrient supplement to be
CD009755. [DOI: 10.1002/14651858.CD009755] [PMID: 22419344] used in pilot programmes among pregnant women in
developing countries: report of a United Nations Children's
SPRING/USAID 2017 Fund (UNICEF), World Health Organization (WHO) and United
Strengthening Partnerships, Results, and Innovations in Nations University workshop. apps.who.int/iris/bitstream/
Nutrition Globally (SPRING), USAID. Six key actions to handle/10665/75358/UNICEF-WHO-multi-micronutrients.pdf?
reduce anaemia from learning to practice; September 2017. sequence=1&isAllowed=y (accessed 25 June 2018).
www.spring-nutrition.org/publications/briefs/six-key-actions-
Van Sande 2013
reduce-anemia.
Van Sande H, Jacquemyn Y, Karepouan N, Ajaji M. Vitamin B12
Stevens 2013 in pregnancy: maternal and fetal/neonatal effects—a review.
Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Open Journal of Obstetrics and Gynecology 2013;3(7):599-602.
Flaxman SR, Branca F, et al. Global, regional, and national [DOI: 10.4236/ojog.2013.37107]
trends in haemoglobin concentration and prevalence of total
Verhagen 1998
and severe anaemia in children and pregnant and non-pregnant
women for 1995-2011: a systematic analysis of population- Verhagen AP, De Vet HC, De Bie RA, Kessels AG, Boers M,
representative data. Lancet Global Health 2013;1(1):e16-25. Bouter LM, et al. The Delphi list: a criteria list for quality
[DOI: 10.1016/S2214-109X(13)70001-9] [PMC4547326] [PMID: assessment of randomized clinical trials for conducting
25103581] systematic reviews developed by Delphi consensus. Journal
of clinical epidemiology 1998;51(12):1235-41. [DOI: 10.1016/
Stoltzfus 1998 s0895-4356(98)00131-0] [PMID: 10086815]
Stoltzfus RJ, Dreyfuss ML, editor(s), International Nutritional
Walker 2010
Anemia Consultative Group (INACG), World Health Organization
(WHO), United Nations Childrens Fund (UNICEF). Guidelines Walker N, Fischer-Walker C, Bryce J, Bahl R, Cousens S, CHERG
for the Use of Iron Supplements to Prevent and Treat Iron Review Groups on Intervention Effects. Standards for CHERG
(Review)
Informed decisions.
reviews of intervention effects on child survival. International WHO 2016a

Journal of Epidemiology 2010;39(Suppl 1):i21-31. [DOI: 10.1093/ World Health Organization. Guideline: Daily Iron
ije/dyq036 ] [PMCID: PMC2845875] [PMID: 20348122 ] Supplementation in Infants and Children. Geneva: World Health
Organization, 2016. [ISBN 978 92 4 154952 3] [apps.who.int/
Wegewitz 2016
iris/bitstream/handle/10665/204712/9789241549523_ eng.pdf?
Wegewitz U, Weikert B, Fishta A, Jacobs A, Pieper D. Resuming sequence=1]
the discussion of AMSTAR: what can (should) be made better?
BMC Medical Research Methodology 2016;16(1):111. [DOI: WHO 2016b
10.1186/s12874-016-0183-6] [PMC5002206] [PMID: 27566440] World Health Organization. Guideline: Daily Iron
Supplementation in Adult Women and Adolescent
Weiss 2005
Girls. Geneva: World Health Organization, 2016. [ISBN
Weiss G, Goodnough LT. Anemia of chronic disease. New 978 92 4 151019 6] [apps.who.int/iris/bitstream/
England Journal of Medicine 2005;352(10):1011-23. [DOI: handle/10665/204761/9789241510196_ eng.pdf?sequence=1]
10.1056/NEJMra041809] [PMID: 15758012]
WHO 2016c
WHO/CDC 2007
World Health Organization. WHO Recommendations
World Health Organization, Centers for Disease Control and on Antenatal Care for a Positive Pregnancy Experience.
Prevention. Assessing the Iron Status of Populations. 2nd Geneva: World Health Organization, 2016. [ISBN
edition. Geneva: World Health Organization, 2007. [ISBN 978 92 4 154991 2] [apps.who.int/iris/bitstream/
978 92 4 159610 7] [www.who.int/nutrition/publications/ handle/10665/250796/9789241549912-eng.pdf?sequence=1]
micronutrients/anaemia_ iron_ deficiency/9789241596107.pdf]
WHO 2016d
WHO/CDC 2008
World Health Organization. WHO Guideline: Fortification of
World Health Organization, Centers for Disease Control and Maize Flour and Corn Meal with Vitamins and Minerals. Geneva:
Prevention. Worldwide Prevalence of Anaemia 1993–2005: World Health Organization, 2016. [ISBN-13: 978-92-4-154993-6]
WHO Global Database on Anaemia. Geneva: World Health [www.ncbi.nlm.nih.gov/books/NBK402401/] [PMID: 28045477]
Organization, 2008. [ISBN 978 92 4 159665 7] [apps.who.int/
iris/bitstream/handle/10665/43894/9789241596657_ eng.pdf? WHO 2017
sequence=1] World Health Organization. Nutritional Anaemias:
Tools for Effective Prevention and Control.
WHO/FAO 2006
Geneva: World Health Organization, 2017. [ISBN
World Health Organization, Food and Agriculture Organization 978-92-4-151306-7] [http://apps.who.int/iris/bitstream/
of the United Nations. Guidelines on Food Fortification handle/10665/259425/9789241513067-eng.pdf?sequence=1]
with Micronutrients. Geneva: World Health Organization,
2006. [ISBN 92 4 159401 2] [apps.who.int/iris/bitstream/ WHO 2020a
handle/10665/43412/9241594012_ eng.pdf?sequence=1] World Health Organization. Anaemia in women of reproductive
age. www.who.int/data/gho/data/themes/topics/indicator-
WHO 2011
groups/indicator-group-details/GHO/prevalence-of-anaemia-in-
World Health Organization. Haemoglobin concentrations for the women-of-reproductive-age (accessed 10 June 2021).
diagnosis of anaemia and assessment of severity. www.who.int/
vmnis/indicators/haemoglobin/en/ (accessed 15 September WHO 2020b
2020). World Health Organization. Prevalence of anaemia in children
aged 6–59 months. www.who.int/data/gho/data/indicators/
WHO 2014a
indicator-details/GHO/prevalence-of-anaemia-in-children-
World Health Organization. Global nutrition targets 2025: under-5-years-(-) (accessed 10 June 2021).
to improve maternal, infant and young child nutrition.
www.who.int/nutrition/global-target-2025/en/ (accessed 25 Yusoff 2012
June 2018). Yusoff H, Daud WN, Ahmad Z. Nutrition education and
knowledge, attitude and hemoglobin status of Malaysian
WHO 2014b
adolescents. Southeast Asian Journal of Tropical Medicine and
World Health Organization. Global nutrition targets Public Health 2012;43(1):192-200. [PMID: 23082570]
2025: anaemia policy brief. apps.who.int/iris/bitstream/
handle/10665/148556/WHO_ NMH_ NHD_ 14.4_ eng.pdf? Zamalloa 2017
sequence=1 (accessed 25 June 2018). Zamalloa CO, Fuentes MS, Valladares DM. The impact of
counseling and education on incidence rates of anemia and iron
WHO 2015
deficiency in children under 3 years. PROSPERO 2017. [Available
World Health Organization. The Global Prevalence of from www.crd.york.ac.uk/prospero/display_ record.php?
Anaemia in 2011. Geneva: World Health Organization, 2015. ID=CRD42017064706] [CRD42017064706]
[ISBN 978 92 4 156496 0 ] [apps.who.int/iris/bitstream/
handle/10665/177094/9789241564960_ eng.pdf?sequence=1]
(Review)
Informed decisions.
Zandonadi 2017 Zimmermann 2007

Zandonadi R, Lima V, Pineli L, Chiarello M. Food strategy for Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet
the prevention and treatment of iron deficiency anemia in 2007;370(9586):511-20. [DOI: 10.1016/S0140-6736(07)61235-5]
childhood: a systematic review. PROSPERO 2017. [Available [PMID: 17693180]
from: www.crd.york.ac.uk/prospero/display_ record.php?
ID=CRD42017075195] [CRD42017075195]
References to other published versions of this review
Zhang 2021
Da Silva Lopes 2018
Zhang YY, Stockmann R, Ng K, Ajlouni S. Opportunities for plant-
Da Silva Lopes K, Takemoto Y, Garcia-Casal MN, Ota E. Nutrition-
derived enhancers for iron, zinc, and calcium bioavailability: a
specific interventions for preventing and controlling anaemia
review. Comprehensive Reviews in Food Science and Food Safety
throughout the life cycle: an overview of systematic reviews.
2021;20(1):652-85. [DOI: 10.1111/1541-4337.12669] [PMID:
Cochrane Database of Systematic Reviews 2018, Issue 8. Art. No:
33443794]
CD013092. [DOI: 10.1002/14651858.CD013092]
ADDITIONAL TABLES
Table 1. Unused methods

Section in the protocol Planned method in the protocol (Da Silva Lopes 2018) Reason for non-use
(Da Silva Lopes 2018)
Data extraction and Where any information from the reviews is unclear or missing, We planned to request the informa-
management we will access the published papers of the individual trials. If tion from the individual review authors
we cannot obtain the details from the published papers, we will or authors of the original papers if we
request the information from the individual review authors or could not obtain the details from the
authors of the original papers. published papers, but this was not
necessary.
Table 2. Excluded reviews: reasons for exclusion

Review Title Reason for exclusion
Agha 2014 Interventions to reduce and prevent obesity in pre-conceptual No relevant outcomes for anaemia
and pregnant women: a systematic review and meta-analysis
Allen 2009 Provision of multiple rather than two or fewer micronutrients Methodological quality of trials was
more effectively improves growth and other outcomes in mi- not assessed, making it difficult to in-
cronutrient-deficient children and adults terpret the results
Ashman 2017 The effectiveness of nutrition interventions for pregnant indige- No relevant outcomes for anaemia
nous women: a systematic review
Athe 2014 Impact of iron-fortified foods on Hb concentration in children (< Methodological quality of trials was
10 years): a systematic review and meta-analysis of randomized not assessed, making it difficult to in-
controlled trials terpret the results
Athe 2020 Meta-analysis approach on iron fortification and its effect on Methodological quality of trials was
pregnancy and its outcome through randomized, controlled tri- not assessed, making it difficult to in-
als terpret the results
Bairwa 2017 Directly observed iron supplementation for control of iron defi- Methodological quality of trials was
ciency anemia not assessed, making it difficult to in-
terpret the results
Best 2011 Can multi-micronutrient food fortification improve the mi- Methodological quality of trials was
cronutrient status, growth, health, and cognition of school- not assessed, making it difficult to in-
children? A systematic review terpret the results
(Review)
Informed decisions.
Table 2. Excluded reviews: reasons for exclusion (Continued)
Brown 2009 Preventive zinc supplementation among infants, preschoolers, Methodological quality of trials was
and older prepubertal children not assessed, making it difficult to in-
terpret the results
Butler 2006 Oral vitamin B12 versus intramuscular vitamin B12 for vitamin Systematic review included partici-
B12 deficiency: a systematic review of randomized controlled pants with megaloblastic anaemia,
trials which was outside the scope of this
overview of reviews
Cancelo-Hidalgo 2013 Tolerability of different oral iron supplements: a systematic re- Included different trial designs and re-
view sults have not been presented sepa-
rately
Câmara 2011 The use of games in health education in order to prevent iron No relevant outcomes for anaemia
deficiency anemia in infancy: the role of the nurse - literature
systematic review
Chang 2018 Safety and tolerability of prescription omega-3 fatty acids: a Systematic review included partici-
systematic review and meta-analysis of randomized controlled pants with dyslipidaemia, which was
trials outside the scope of this overview of
reviews
Da Cunha 2019 Effect of vitamin A supplementation on iron status in humans: a Included different trial designs and re-
systematic review and meta-analysis sults have not been presented sepa-
rately
Das 2013b Micronutrient fortification of food and its impact on woman Included different trial designs and re-
and child health: a systematic review sults have not been presented sepa-
rately
De Barros 2016 Adherence to and acceptability of home fortification with vita- No relevant outcomes for anaemia
mins and minerals in children aged 6 to 23 months: a systemat-
ic review
Dror 2012 Interventions with vitamins B6, B12 and C in pregnancy No relevant outcomes for anaemia
Eaton 2019 Effectiveness of provision of animal-source foods for sup- No relevant outcomes for anaemia
porting optimal growth and development in children 6 to 59
months of age
Falkingham 2010 The effects of oral iron supplementation on cognition in older No relevant outcomes for anaemia
children and adults: a systematic review and meta-analysis
Fishman 2000 The role of vitamins in the prevention and control anaemia Methodological quality of trials was
not assessed, making it difficult to in-
terpret the results
Gavaravarapu 2017 Role of education and communication interventions in promot- Methodological quality of trials was
ing micronutrient status in India – what research in the last two not assessed, making it difficult to in-
decades informs terpret the results
Ghanchi 2019 Guts, germs, and iron: a systematic review on iron supplemen- No relevant outcomes for anaemia
tation, iron fortification, and diarrhea in children aged 4-59
months
Gera 2007b Effect of iron supplementation on physical performance in chil- No relevant outcomes for anaemia
dren and adolescents: systematic review of randomized con-
trolled trials
(Review)
Informed decisions.
Girard 2012a Nutrition education and counselling provided during pregnan- Included different trial designs and re-
cy: effects on maternal, neonatal and child health outcomes sults have not been presented sepa-
rately
Girard 2012b The effects of household food production strategies on the Included different trial designs and re-
health and nutrition outcomes of women and young children: a sults have not been presented sepa-
systematic review rately
Guo 2015 Daily iron supplementation on cognitive performance in pri- No relevant outcomes for anaemia
mary-school-aged children with and without anemia: a meta-
analysis
Gurusamy 2014 Iron therapy in anaemic adults without chronic kidney disease Systematic review included non-
healthy participants, which was out-
side the scope of this overview of re-
views
Haider 2018 The effect of vegetarian diets on iron status in adults: a system- Included different trial designs and re-
atic review and meta-analysis sults have not been presented sepa-
rately
Kong 2016 Limitations of studies on school-based nutrition education in- Included different trial designs and re-
terventions for obesity in China: a systematic review and meta- sults have not been presented sepa-
analysis rately
Iannotti 2006 Iron supplementation in early childhood: health benefits and Systematic review included high-risk
risks populations (e.g. participants with HIV,
tuberculosis), which was outside the
scope of this overview of reviews
Iglesias 2019 Prevalence of anemia in children from Latin America and the Included different trial designs and re-
Caribbean and effectiveness of nutritional interventions: sys- sults have not been presented sepa-
tematic review and meta-analysis rately
Iqbal 2019 Maternal and neonatal outcomes related to iron supplementa- Overview of systematic reviews
tion or iron status: a summary of meta-analyses
Jackson 2016 Is higher consumption of animal flesh foods associated with Included different trial designs and re-
better iron status among adults in developed countries? A sys- sults have not been presented sepa-
tematic review rately
Lewkowitz 2019 Intravenous compared with oral iron for the treatment of iron- Methodological quality of trials was
deficiency anemia in pregnancy: a systematic review and meta- not assessed, making it difficult to in-
analysis terpret the results
Lohner 2012 Effect of folate supplementation on folate status and health Methodological quality of trials was
outcomes in infants, children and adolescents: a systematic re- not assessed, making it difficult to in-
view terpret the results
Martínez 2020 Efficacy and tolerability of oral iron protein succinylate: a sys- Included different trial designs and re-
tematic review of three decades of research sults have not been presented sepa-
rately
Mayo-Wilson 2014b Preventive zinc supplementation for children, and the effect of Systematic review published as a
additional iron: a systematic review and meta-analysis Cochrane Review, Mayo-Wilson 2014a,
which has been included in this
overview of reviews
(Review)
Informed decisions.
McDonagh 2015a Routine iron supplementation and screening for iron deficien- Included different trial designs and re-
cy anemia in children ages 6 to 24 months: a systematic review sults have not been presented sepa-
to update the US Preventive Services Task Force Recommenda- rately
tion
McDonagh 2015b Routine iron supplementation and screening for iron deficiency Included different trial designs and re-
anemia in pregnant women: a systematic review to update the sults have not been presented sepa-
US Preventive Services Task Force Recommendation rately
McDonagh 2015c Screening and routine supplementation for iron deficiency ane- Included different trial designs and re-
mia: a systematic review sults have not been presented sepa-
rately
Michelazzo 2013 The influence of vitamin A supplementation on iron status Methodological quality of trials was
not assessed, making it difficult to in-
terpret the results
Middleton 2013 Nutrition interventions and programs for reducing mortality Included different trial designs and re-
and morbidity in pregnant and lactating women and women of sults have not been presented sepa-
reproductive age: a systematic review rately
Middleton 2018 Omega-3 fatty acid addition during pregnancy No relevant outcomes for anaemia
Miles 2019 Intravenous iron therapy for non-anaemic, iron-deficient adults Systematic review included high-risk
populations (not-healthy participants),
which was outside the scope of this
overview of reviews
Milne 2009 Protein and energy supplementation in elderly people at risk No relevant outcomes for anaemia
from malnutrition
Mirmiran 2012 Iron, iodine and vitamin a in the middle East; a systematic re- Included different trial designs and re-
view of deficiency and food fortification sults have not been presented sepa-
rately
Oddo 2019 Potential interventions targeting adolescent nutrition in In- Methodological quality of trials was
donesia: a literature review not assessed, making it difficult to in-
terpret the results
Oh 2020 Vitamin and mineral supplementation during pregnancy on Included different trial designs and re-
maternal, birth, child health and development outcomes in sults have not been presented sepa-
low- and middle-income countries: a systematic review and rately
meta-analysis
Oliveira 2016 Vitamin A supplementation for postpartum women No relevant outcomes for anaemia
Osungbade 2012 Preventive treatments of iron deficiency anaemia in pregnancy: Included different trial designs and re-
a review of their effectiveness and implications for health sys- sults have not been presented sepa-
tem strengthening rately
Pachón 2015 Evidence of the effectiveness of flour fortification programs on Included different trial designs and re-
iron status and anemia: a systematic review sults have not been presented sepa-
rately
Pasricha 2009 Risks of routine iron and folic acid supplementation for young No relevant outcomes for anaemia
children
(Review)
Informed decisions.
Pasricha 2014 Iron supplementation benefits physical performance in women No relevant outcomes for anaemia
of reproductive age: a systematic review and meta-analysis
Sachdev 2005 Effect of iron supplementation on mental and motor develop- No relevant outcomes for anaemia
ment in children: systematic review of randomised controlled
trials
Sguassero 2012 Community-based supplementary feeding for promoting the No relevant outcomes for anaemia
growth of children under five years of age in low and middle in-
come countries
Shao 2019 The efficacy of ferumoxytol for iron deficiency anemia: a meta- Systematic review included high-risk
analysis of randomized controlled trials populations (cancer patients), which
was outside the scope of this overview
of reviews
Smith 2017 Modifiers of the effect of maternal multiple micronutrient sup- No relevant outcomes for anaemia
plementation on stillbirth, birth outcomes, and infant mor-
tality: a meta-analysis of individual patient data from 17 ran-
domised trials in low-income and middle-income countries
Sun 2018 Effect of dietary intervention treatment on children with iron Methodological quality of trials was
deficiency anemia in China: a meta-analysis not assessed, making it difficult to in-
terpret the results
Szajewska 2010 Effects of iron supplementation in nonanemic pregnant No relevant outcomes for anaemia
women, infants, and young children on the mental perfor-
mance and psychomotor development of children: a systemat-
ic review of randomized controlled trials
Tam 2020 Micronutrient supplementation and fortification interventions Methodological quality of trials was
on health and development outcomes among children un- not assessed, making it difficult to in-
der-five in low- and middle-income countries: a systematic re- terpret the results
view and meta-analysis
Vonderheid 2019 A systematic review and meta-analysis on the effects of probi- Included different trial designs and re-
otic species on iron absorption and iron status sults have not been presented sepa-
rately
Xu 2019 Supplementing fortified soybean powder reduced anemia in in- Included different trial designs and re-
fants and young children aged 6-24months sults have not been presented sepa-
rately
Yadav 2020 Comparison of different doses of daily iron supplementation for Methodological quality of trials was
anemia prophylaxis in pregnancy: a systematic review not assessed, making it difficult to in-
terpret the results
(Review)
(Review)
Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of systematic reviews
Table 3. Characteristics of included systematic reviews: infants (aged 6 to 23 months)
Review Date of Number Review ques- Trial de- Partici- Setting, Intervention Relevant GRADE assessment of
search of includ- tion/objective signs in- pants anaemia and and compari- outcomes relevant outcomes
Library
Cochrane
ed trials cluded malaria preva- son (definition
(number lence used in the Method used to assess
of partic- review, ad- risk of bias and sum-
ipants in- justed for mary
cluded) smoking
and alti-
Better health.
Informed decisions.
Trusted evidence.
tude)
Supplementation
Abdullah January 2 trials To evaluate RCTs The partici- Turkey, Indone- Intervention: End-of-trial GRADE: not assessed
2013 2011 (249 chil- the efficacy of pants were sia oral Fe therapy levels of Hb
dren) oral Fe thera- Qua- Fe deficient (≥ 2 mg elemen- (g/L)
Efficacy of py in children si-RCTs (serum fer- Anaemia and tal Fe/kg body
oral iron malaria preva- Adjust- Cochrane RoB 1 tool.
of pre-school ritin < 12 μg/ weight per day
therapy in lence: not re- ments: not Both trials were as-
age (1–5 years) L) but non- administered
improving ported reported sessed at moderate risk
with NAID (nor- anaemic for ≥ 3 months)
the devel- of bias
mal Hb, low (Hb > 110 g/ with or without
opmental Fe status) in L) children other interven-
outcome of improving de- who were tions aimed at
pre-school velopmental otherwise improving Fe
children outcomes and healthy and level (such as
with non- to evaluate aged 1–5 dietary coun-
anaemic the efficacy of years selling, vitamin
iron defi- oral Fe thera- C, folic acid)
ciency: a py in terms of
systematic haematologi- Comparison:
review cal outcomes placebo or no
and incidence treatment
of side-effects
of Fe therapy in

children of pre-
school age with
NAID
Das 2019a October 17 trials To assess the RCTs Non-hos- Ghana (2 tri- Intervention: Anaemia (as GRADE: LNS plus com-
2018 (23,200 effects and pitalised als), Malawi (4 LNS with com- defined by plementary feeding
Preven- children) safety of pre- Qua- infants trials), Demo- plementary trialists) compared with no in-
tive lipid- ventive LNS giv- si-RCTs and young cratic Repub- food at point- Any adverse tervention: anaemia
based nutri- en with comple- children lic of Congo, of-use effects, in- = low, adverse effects
ent supplementary foods aged 6 to 23 Bangladesh (3 cluding al- = moderate; LNS plus
ments given on health, nutri- months of trials), Burk- lergic reac- complementary feed-
with com- tion and devel- age in sta- ina Faso, tions, as di-
59
(Review)
Table 3. Characteristics of included systematic reviews: infants (aged 6 to 23 months) (Continued)
plementary opmental out- ble (i.e. not Chad, Haiti, Comparison: no agnosed by ing compared with MNP:
foods to in- comes of non- in any emer- Peru, Kenya, intervention, clinical as- anaemia = low
Library
Cochrane
fants and hospitalised in- gency-af- Guatemala, and placebo, or sessment
young chil- fants and chil- fected coun- the south-west- compared with (atopic der-
dren 6 to dren 6 to 23 try or emer- ern part of In- other foods/ matitis,
Cochrane RoB 1 tool.
23 months months of age, gency set- tibucá, Hon- supplements or urticaria,
Overall, most trials were
of age for and whether tings ac- duras, border- nutrition inter- oedema
at low risk of bias for
health, nu- or not they are cording to ing El Salvador vention (oral), oph-
random sequence gen-
trition, and more effec- WHO defini- thalmic pru-
Better health.
Informed decisions.
Trusted evidence.
Anaemia and eration, allocation con-
develop- tive than other tion) ritus, aller-
malaria preva- cealment, blinding of
mental out- foods, including gic rhini-
lence: not re- outcome assessment,
comes FBF or MNP tis, asthma,
ported incomplete outcome
anaphylax-
data, selective report-
is)
ing and other sources
Adjust- of bias. Most trials were
ments: not assessed at high risk of
reported bias for blinding of par-
ticipants and personnel
due to the nature of the
intervention.
Dekker 2010 May 2009 21 trials To evaluate RCTs Apparently Latin America (8 Intervention: Hb (g/L) GRADE: not assessed
(3869 chil- the effect of healthy chil- trials), Africa (3 zinc supple-
Zinc supple- dren) zinc supple- dren from trials), Asia (10 mentation Adjust-
mentation mentation on birth-15 trials) ments: not
in children Comparison: reported Jadad level-of-evidence
haemoglobin years
is not asso- Anaemiac and placebo score for RCTs. 11 trials
concentrations
ciated with (mean age malaria preva- with high Jadad scores
among appar-
decreases in ently healthy at baseline = lence: 3 trials
hemoglobin children 32 months, were conducted
concentra- the major- among anaemic

tions ity of tri- children and 3
als com- among children
menced be- with malaria
tween 6-23
months)
Pasricha February 33 trials To review the RCTs Healthy Benin, Chile, Intervention: Hb (g/L) GRADE: not assessed
2013 2013 (42,015 evidence for children Costa Rica, daily oral iron
children) benefit and Clus- aged 4–23 France, Ghana, supplementa- Anaemia
Effect of dai- safety of dai- ter-RCTs months Guatemala, In- tion (alone or (defined by
ly iron sup- trial investi- Cochrane RoB 1 tool.
ly iron supple- dia (2 trials), with co-inter-
plemen- Qua- gators) Many trials did not ade-
mentation in Indonesia (5 vention)
si-RCTs
60
(Review)
tation on children aged trials), Kenya, Comparison: IDA (defined quately report method-
health in 4–23 months Nepal (2 trials), control or co- by trial in- ology for
Library
Cochrane
children Pakistan, Swe- intervention vestigators) randomisation and con-
aged 4-23 den and Hon- alone cealment of allocation,
months: a duras, Tanza- ID and only
systemat- nia (2 trials), 9 trials were considered
Adverse ef-
ic review Thailand, Togo, at low risk of bias
fect (any
and meta- Turkey (4 trials),
side effects,
analysis of UK, USA (6 tri-
Better health.
Informed decisions.
Trusted evidence.
vomiting,
randomised als), Vietnam (2
diarrhoea,
controlled trials)
constipa-
trials
Anaemia and tion)
malaria preva-
Adjust-
lence: some tri-
ments: not
als conducted
reported
in malaria-en-
demic areas
Petry 2016b October 90 trials To evaluate the RCTs Pregnant Not described Intervention: Hb (g/dL) GRADE: Hb = moder-
2015 potential of in- women or iron or zinc ate, anaemia = low, IDA
The effect terventions de- Qua- lactating supplementa- Anaemia (%; = high, ID = high, diar-
of low dose livering daily si-RCTs women, tion, fortifica- defined as rhoea = not assessed
iron and doses of iron children tion or bioforti- Hb < 110 g/
zinc intake (and qua- L)
and zinc in con- aged 6–23 fication
on child mi- si exper-
centrations up months
cronutri- imental, Comparison in IDA (%; de- Assessment based on
to approximate-
ent status but rarely ; 74 trials fortification tri- fined as Hb random sequence gen-
ly the RNI in di-
and devel- included) included als: unfortified < 105 g/L or eration, adequacy of
ets with low
opment dur- children, 17 foods or regular < 110 g/L blinding of trial partici-
bioavailability Clus-
ing the first pregnant diets, same mi- and serum pants and personnel and
during the first ter-RCTs
1000 days women, 1 cronutrient but ferritin < 10 completeness of out-
1000 days of
of life: a sys- lactating without iron or μg/L or < 12 comes assessment. On-
life on child mi-
tematic re- women zinc μg/L) ly GRADE results are pre-
cronutrient sta-

view and sented
tus and health ID (%; de-
meta-analy- Comparison in
supplementa- fined as
sis
tion trials: no serum fer-
supplements, ritin < 10 μg/
placebo, a low- L or < 12 μg/
er concentra- L)
tion of iron or
Diarrhoea
zinc, same mi-
cronutrients Adjust-
without iron or ments: not
zinc reported
61
(Review)
Data only
available for
Library
Cochrane
children and
iron inter-
ventions
Pratt 2015 October 8 trials To compare RCTs 6 and 36 Mexico (3 tri- Interventions: Hb (g/L) GRADE: not assessed
2014 (8109 chil- the effective- Clus- months of als), Cambo- any strategy or Anaemia (as
A review of dren) ness of several ter-RCTs age, dia (1 trial), The method used defined by
Better health.
Informed decisions.
Trusted evidence.
the strate- strategies used either Kyrygyz Re- to reduce the trialists)
gies used Ran- Modified Critical Ap-
to reduce the healthy or public (1 trial), prevalence of ID ID (as de-
to reduce domised praisal Skills Pro-
prevalence of diagnosed Brazil (1 trial), and IDA fined by tri-
the preva- effective- gramme (CASP) tool. In
ID and IDA in in- with ID or USA (1 trial), alists, based
lence of iron ness trial Comparison: all trials, participants
fants aged 6–36 IDA New Zealand (1 on
deficien- control or oth- were randomised to
months trial) biomarker
cy and iron er current reg- treatments and were
of iron sta-
deficiency Anaemia and imens to in- blinded
tus, e.g. fer-
anaemia in malaria preva- crease Hb sta- ritin <
infants aged lence: not re- tus and reduce 12 lg/L for
6-36 months ported the prevalence preschool
of ID and IDA children)
Fortification
Dewey 2009 November 16 trials To evaluate the RCTs Infant and Ghana (5 tri- Intervention: Hb (g/L) GRADE: not assessed
2007 (6113 chil- efficacy and ef- young als), China (2 home fortifi-
Systematic dren) fectiveness of Clus- children trials), India (1 cation of com- Anaemia
review and home fortifica- ter-RCTs (anaemic trial), Mongolia plementary (Hb < 100 g/
meta-analy- L) Tool used to assess
tion of comple- at baseline (1 trial), South foods with
sis of home (2 non- risk of bias was not de-
mentary foods in treat- Africa (1 trial), MNPs (sprin-
fortification ran- ID (ferritin < scribed. 7 trials were rat-
ment trials Bangladesh (1 kles), crush-
of comple- domised 12 μg/L) ed at low risk of bias, 5
and non- trial), Pakistan able tablets
mentary trials) at very low risk of bias
anaemic in (1 trial), Canada and lipid-based Diarrhoea and 1 at high risk of bias.

foods prevention (1 trial), Cam- or soy-based
1 non-randomised tri-
trials) bodia (1 trial), products Adjust-
al was rated at low risk
Malawi (1 trial), ments: not
Comparison: of confounding and 1
Haiti (1 trial) reported
non-interven- of moderate risk of con-
Malaria preva- tion group or founding.
lence: several placebo or for-
trials conduct- tified wheat
ed in popula- soy blend with-
tions with high out sprinkles
rates of malaria or iron drops or
complementary
62
(Review)
foods alone or
sprinkles iron
Library
Cochrane
only
Eichler 2012 February 18 trials To specifical- RCTs Infants Asia (2 trials), Intervnetion: Hb (g/dL) GRADE: not assessed
2011 (5468 in- ly assess the and chil- Africa (5 trials), micronutri-
Effects of fants and impact of mi- Clus- dren from 6 South and Mid- ent-fortified Anaemia
micronutri- children) cronutrient for- ter-RCTs months to 5 dle America (5 milk or cereal
ent fortified Adjust- Cochrane RoB 1 tool.
tified milk and years of age. trials), Europa food
Better health.
Informed decisions.
Trusted evidence.
milk and ce- ments: not Only 2 trials were rat-
cereal food on Mean age of (6 trials)
real food for Comparison: reported ed at low risk of bias for
the health of in- participants
infants and Anaemia and non-fortified random sequence gen-
fants and chil- ranged
children: a malaria preva- food; addition- eration and allocation
dren compared from 6 to 23
systematic lence: not real, other nu- concealment. Blinding
to non-fortified months at
review ported tritional ap- was rated at low risk in
food in RCTs inclusion
proaches, if 13 trials
such approach-
es were applied
in the interven-
tion and control
group
Matsuyama June 2014 15 trials To investigate RCTs Children Low-income to Intervention: Hb (g/L) GRADE: not assessed
2017 the effect of (mean age high-income fortified milk
fortified milk Clus- at baseline economies Anaemia
Effect of for- products com- ter-RCTs = 6 to 22.4 (India, In- Comparison: (Hb < 110 g/
tified milk cow's milk or L) Cochrane RoB 1 tool.
pared with months, 1 donesia, Mex-
on growth non- or low-for- About two-thirds of the
control milk trial = 29 to ico, Vietnam,
and nutri- tified milk Adjust- trials were adequate for
in young chil- 31 months Malysia, Thai-
tional sta- ments: not random sequence gen-
dren's growth at baseline) land, Nether-
tus in young reported eration, allocation con-
and nutrition- lands, Poland,
children: a cealment and blinding.
al status out- Portugal, UK,
systematic come, such as Sweden, New
review and body size and Zealand)

meta-analy- composition,
sis and/or bio- Anaemia and
chemical mark- malaria preva-
ers lence: not re-
ported
Salam 2013 November 17 trials To estimate the RCTs Children Low-income Intervention: Hb (g/L) GRADE: Hb = moder-
2012 effect of MNPs aged 6 countries MNP ate, anaemia = moder-
Effective- on the health Clus- months to Anaemia ate, IDA = moderate, di-
ness of mi- outcomes of ter-RCTs 11 years Anaemia and Comparison: no arrhoea = moderate,
cronutri- malaria preva- intervention or IDA
women and (most trials recurrent diarrhoea =
ent pow- children 6 months control moderate
63
(Review)
ders (MNP) to 6 years, 2 lence: not re- Diarrhoea
in women trials up to ported
Adjust- Each trial was assessed
Library
Cochrane
and children 11 years)
ments: not and graded according to
*50% of the reported the CHERG adaptation of
trials were the GRADE technique
conducted
in children
aged 6 to
Better health.
Informed decisions.
Trusted evidence.
23 months,
75% of the
trials were
conduct-
ed chil-
dren aged 6
months to 6
years
Suchdev July 2019 29 trials To assess the RCTs Infants Low-income Intervention: Hb (g/L) GRADE: MNP versus
2020 (33,147 effects and and young countries in MNPs includ- placebo or no interven-
partici- safety of home Clus- children Asia, Africa and ing at least the Anaemia tion: Hb = low, anaemia
Home forti- pants) (point-of-use) ter-RCTs aged 6 to the Caribbean 3 micronutri- = moderate, ID = high;
fication of (defined as
fortification 23 months where anaemia ents iron, zinc MNP versus iron supple-
foods with Qua- Hb values
of foods with at the start is a public and vitamin A ments intervention: Hb =
multiple mi- si-RCTs lower than
multiple MNPs) of the in- health problem (given to whole very low, anaemia = low
cronutrient 110 g/L)
on nutrition, tervention (that is, > 40% families, added
powders for health, and de- (apparently of the popula- to the family ID (defined
health and velopmental healthy chil- tion are affect- meal) by trialists) Cochrane RoB 1 tool.
nutrition outcomes dren from ed)
in children Comparison: no Overall, random se-
in children un- the general Diarrhoea
under two Malaria preva- intervention, quence generation was
der two years of population,
years of age lence: 27 trials placebo or usu- Side effects adequate in 22 trials and
age although
conducted in al supplemen- (such as allocation concealment
some may
malaria-endem- tation: 1) home staining of in 21 trials. 10 trials were
be at risk of

ic areas (point-of-use) teeth, vom- at high risk of bias for
having high-
fortification of iting, stool blinding of participants
ly preva-
foods with MNP discoloura- and personnel and 9 for
lent dis-
versus no in- tion, con- blinding of outcome as-
eases such
tervention or stipation, sessment.
as malaria,
diarrhoea or placebo; 2) ver- coughing)
even under- sus iron-only
nutrition) supplement; Adjust-
3) versus iron ments: not
and folic acid reported
supplements; 4)
versus the same
64
(Review)
multiple mi-
cronutrients as
Library
Cochrane
in supplements
Kristjansson January 32 trials To assess the RCTs Children 29 trials were Intervention: Hb GRADE: not assessed for
2015 2014 (21 RCTs effectiveness of aged 3 from low- and supplementary relevant outcomes
and 11 supplementary Cluster months to 5 middle-income feeding (provi- Anaemia
Better health.
Informed decisions.
Trusted evidence.
Food sup- CBAs) feeding inter- RCTs years; > 60% countries; 3 sion of energy (CBAs on-
plemen- ventions, alone of children were from high- and macronu- ly) Adjust-
tation for CBAs ments: not Cochrane RoB 1 tool.
or with co-in- were under income coun- trients) with or
improving reported The quality of RCTs was
tervention, for (data ex- 2 years tries without added
the physi- moderate. Attrition bias
improving the tracted for micronutrients
cal and psy- Anaemia and was problematic, rang-
physical and RCTs only)
chosocial malaria preva- Comparison: ing from 1% to 78%.
psychosocial
health of so- lence: not re- non-feeding Many trials did not men-
health of dis-
cio-econom- ported control tion blinding.
advantaged
ically disad- children aged
vantaged 3 months to 5
children years
aged three
months to
five years
Shapiro June 2017 21 studies To examine the RCTs Children Low-income Intervention: Hb GRADE: not assessed
2019 (7 RCTs, relation be- aged 6 to countries: 10 consumption of
7 cross- tween ASF con- Cross- 60 months trials ASFs Anaemia ad-
A systemat- sectional sumption and sectional (RCTs: 6 to justments:
ic review in- studies Low-middle in- Comparison: not reported Quality assessment
studies, 7 stunting in chil- 9 months)
vestigating come countries: comparator or tools from the NHLBI:
longitudi- dren aged 6–60 in low- and
the relation Longitudi- 7 trials control group NHLBI Quality Assess-
nal cohort months in low- middle-in-
between an- nal cohort (e.g. non-ASF, ment of Controlled In-
studies) and middle-income coun-
imal-source studies Upper-middle such as a PSF, tervention Studies,

come countries. tries
food con- income coun- or no interven- NHLBI Quality Assess-
(data ex- tries: 3 trials ment Tool for Observa-
sumption To examine the tion)
tracted for tional Cohort and Cross-
and stunt- relation be-
RCTs only) Multi-site tri- Sectional Studies. Three
ing in chil- tween ASF con-
al conducted of the 7 RCTs were rated
dren aged sumption and
in 4 countries as good, 2 were rated as
6-60 months other indicators
(1 low and 3 fair, and 2 were rated as
in low and of growth and
middle-income poor.
middle-in- development
countries): 1
come coun- (length/height,
trial (malaria
tries weight, head
treatment re-
circumference,
ported in one
and anaemia)
65
(Review)
trial, anaemia
prevalence not
Library
Cochrane
reported)
ASF: animal-source foods; CBA: controlled before-after trials; CASP: Critical Appraisal Skills Programme; CHERG: Child Health Epidemiology Reference Group; FBF: fortified
blended foods; Fe: chemical symbol for iron; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; LNS: lipid-based nutrient supplements; MNP: micronutrient
powder; NAID: non-anaemic iron deficiency; NHLBI: National Heart, Lung, and Blood Institute; PSF: plant-source foods; RCTs: randomised controlled trials; RNI: recommended
nutrient intake; WHO: World Health Organization.
Better health.
Informed decisions.
Trusted evidence.
Table 4. Characteristics of included systematic reviews: preschool and school-aged children (aged 2 to 10 years)
Review Date of Number Review ques- Trial de- Partici- Setting, Interven- Relevant out- GRADE assessment of rele-
search of includ- tion/objec- signs in- pants anaemia tion and comes (defini- vant outcomes
ed trials tive cluded and malaria comparison tion used in the
(number prevalence review, adjusted Method used to assess risk
of partic- for smoking and of bias and summary
ipants in- altitude)
cluded)
Supplementation
Low 2013 July 2013 32 trials To review of RCTs Primary Low or mid- Interven- Hb (g/L) GRADE: not assessed
(7089 chil- the effects of school– dle-income tion: daily
Effects of dren) daily iron sup- Clus- aged chil- countries, ex- iron supple- Anaemia (Hb < Cochrane RoB 1 tool. On-
daily iron plementation, ter-RCTs dren (5–12 cept for 1 trial mentation 120 g/L or as de- ly 4 trials were considered
supple- a commonly years) fined by trial at low overall risk of bias.
mentation used strate- Malaria: 9 tri- Compari- authors) Many trials did not report
in prima- gy to combat als conducted son: place- the randomisation method
ry-school- in endemic ar- bo or con- IDA (20 trials), allocation con-
anaemia
aged chil- eas trol cealment (25 trials) or blind-
ID
dren: sys- ing (18 trials).
tematic re- Anaemia
Adverse effects

view and prevalence:
(gastrointestinal
meta-analy- not reported
upset, constipa-
sis of ran- tion, vomiting)
domized
controlled Adjustments: not
trials reported
De-Regil May 2011 33 trials To assess the RCTs Children Low and mid- Interven- Hb (g/L) GRADE: intermittent iron
2011 (13,114 effects of in- under 12 dle-income tion: inter- supplementation versus
children) termittent Clus- years of countries in mittent sup- Anaemia (Hb be- placebo or no intervention:
Intermittent iron supple- ter-RCTs age Asia, Africa plementa- low a cut-off de- Hb = low, anaemia = moder-
iron supplementation, tion with fined by trialists, ate, IDA = no data, ID = very
66
(Review)
Table 4. Characteristics of included systematic reviews: preschool and school-aged children (aged 2 to 10 years) (Continued)
mentation alone or in Qua- and Latin iron alone taking into ac- low; intermittent iron sup-
for improv- combination si-RCTs America or with oth- count the age plementation versus daily
Library
Cochrane
ing nutrition with other vi- er nutrients and altitude) iron supplementation: Hb
and devel- tamins and Malaria: 6 tri- = low, anaemia = low, IDA =
opment in minerals, on als conduct- Compari- IDA (defined by no data, ID = very low, other
children un- nutritional ed in endem- son: place- the presence of outcomes = not assessed
der 12 years and develop- ic areas, most bo or no in- anaemia plus ID,
of age mental out- trials did not tervention diagnosed with Cochrane RoB 1 tool. Many
comes in chil- report on or daily sup- an indicator of trials were rated at unclear
Better health.
Informed decisions.
Trusted evidence.
dren from malaria plementa- iron status select- risk of bias for, random se-
birth to 12 tion ed by trialists) quence generation, alloca-
Anaemia tion concealment and attri-
years of age
prevalence: ID (as measured tion rates. In half of the tri-
compared
not reported by trialists by us- als, blinding of participants
with a place-
ing indicators and personnel was rated
bo, no inter-
of iron status, at high risk of bias. Overall,
vention or
such as ferritin or less than one-third of the
daily supple-
transferrin) trials were rated at low risk
mentation
of bias.
Diarrhoea
Any other ad-

verse side effects
(as measured by
trialists, such as
stained teeth,
headache, stom-
ach ache, dis-
comfort, consti-
pation)
Adjustments: not
reported
Mayo-Wil- January 80 trials To assess RCTs Children 73 trials (91%) Interven- Blood Hb concen- GRADE: side effect partic-

son 2014a 2013 (205,401 the effects of aged 6 were conduct- tion: zinc tration ipants with ≥ 1 vomiting
partici- zinc supple- Clus- months to ed in supplemen- episode = high, other out-
Zinc supple- pants) mentation ter-RCTs 12 years of low- or mid- tation Prevalence of comes = not assessed
mentation for prevent- age (mean dle-income anaemia
for prevent- Cross-over Compari- Cochrane RoB 1 tool. One-
ing mortali- age = 28 countries:
ing mortal- RCTs son: place- Prevalence of ID third of the trials were at
ty and mor- months) Asia (37 tri-
ity, morbidity, and als), Latin bo, no inter- low risk of bias for random
Side effects (par-
bidity, and for promot- America and vention sequence generation and
ticipants with ≥ 1
growth fail- ing growth, in the Caribbean allocation concealment.
side effect, vom-
ure in chil- children aged (26 trials) The remaining trials were
iting episodes,
dren aged 6 6 months to and sub-Sa- at unclear risk of bias. 80%
participants with
months to haran Africa of the trials were at low risk
67
(Review)
12 years of 12 years of (10 trials); 7 ≥ 1 vomiting of bias for blinding. Selec-
age age conducted in episode) tive reporting was unclear
Library
Cochrane
North Ameri- in 50% of the trials and high
ca or Europe Adjustments: not risk in 40%.
reported
Anaemia
and malaria
prevalence:
measured in
Better health.
Informed decisions.
Trusted evidence.
some trials,
but not speci-
fied
Thompson April 2012 15 trials To summarise RCTs Children Mainly low- Interven- Hb (g/L) GRADE: Hb = high, anaemia
2013 the evidence from 2 to middle-in- tion: oral = very low
for effects of Clus- 5 years of come coun- iron supple- Anemia (defined
Effects of daily iron sup- ter-RCTs age tries ment by authors) Cochrane RoB 1 tool. 13 tri-
daily iron plementation als at unclear risk of bias
supplemen- Anaemia Compari- Adjustments: not for random sequence gen-
administered
tation in 2- and malaria son: place- reported eration and allocation con-
to children 2
to 5-year- to 5 years of prevalence: bo or other cealment. Blinding was ade-
old children: age 4 trials in supplemen- quate in 11 trials.
systematic malaria en- tations
review and demic areas
meta-analy-
sis
Fortification
Aaron 2015 February 10 trials To evaluate RCTs Apparent- School setting Interven- Hb (g/L) GRADE: Hb = moderate,
2015 (4645 par- the nutrition- ly healthy in low-mid- tion: non- anaemia = moderate, ID =
Multiple-mi- ticipants) al impacts of (school- dle-income dairy MMN- Anaemia (Hb < moderate, IDA = low
cronutri- MMN-fortified aged) chil- countries: fortified 110 to 120 g/L)
ent fortified beverages in dren and Bangladesh, beverages Risk of bias tool not stat-

non-dairy ID (ferritin < 27 to ed, but trial bias was as-
the context women of Botswana,
beverage in- Compar- 45 pmol/L) sessed by publication bias,
of low-mid- reproduc- India, Nige-
terventions dle-income tive age ria, the Philip- ison: iso- randomisation methods,
IDA (Hb < 110 to
reduce the countries pines, South caloric non- type of blinding (single or
120 g/L and fer-
risk of ane- Africa, and fortified, double), the percentage of
ritin < 27 to 45
mia and iron Tanzania non-inter- loss to follow-up (low versus
pmol/L)
deficiency in vention con- high) and subgroup analy-
school-aged Anaemia trols, MMN- Adjustments: not ses. Methodological quality
children in and malaria fortified reported was high in 2 trials, moder-
low-mid- prevalence: non-caloric ate in 7 and low in 1
dle income not reported beverage or
countries: a unfortified
68
(Review)
systematic non-caloric
review and control
Library
Cochrane
meta-analy-
sis
Das 2013a October 11 tri- To assess im- RCTs Woman 4 trials were Interven- Serum haemo- GRADE = not assessed
2012 als (771 pact of food and chil- conducted in tion: forti- globin
Systemat- women fortification Qua- dren (new- low-income fied food Risk of bias tool not stat-
ic review of and chil- with zinc on si-RCTs born, in- countries, with zinc as Adjustments: not ed, but risk of bias was as-
Better health.
Informed decisions.
Trusted evidence.
zinc fortifi- dren) the health fants and while the rest the only mi- reported sessed for the following do-
cation trials and nutrition school- were from cronutrient mains: sequence
of women and aged chil- high-income allocation, allocation
children dren) countries. Compari- concealment, blinding, in-
son: no incomplete outcome data ad-
Hb data Anaemia tervention dressed, selective reporting.
only avail- and malaria group, with In 2 trials, risk of bias was
able for prevalence: a regular di- low; most trials were at un-
school- not reported et or unfor- clear or high risk of bias
aged chil- tified foods
dren
De-Regil December 13 trials To assess RCTs Children Low- and mid- Interven- Hb (g/L) GRADE: Hb = low, anaemia
2017 2016 and (5810 par- the effects aged 24 dle-income tion: provi- = moderate, ID = moderate,
April 2017 ticipants) of point-of- Qua- months (2 populations, sion of MNP Anaemia (defined adverse effects = moderate,
Point-of- use fortifica- si-RCTs years) to with the au- for point-of- as Hb < 110 g/L diarrhoea = low
use fortifi- tion of foods 59 months thors of 7 tri- use fortifica- for children aged
cation of Clus- 24 to 59 months Cochrane RoB 1 tool. 9 of
with iron- (< 5 years als reporting tion given
foods with ter-RCTs and < 115 g/L for the 13 trials were consid-
containing of age) that partici- at any dose,
micronu- MNP alone, or and 5 to pants were of frequency children aged ered at low risk of bias. In
trient pow- in combina- 12 years of low socioeco- and dura- 5 to 11.9 years, most trials, the main limita-
ders con- tion with oth- age at the nomic status tion adjusted by alti- tion was the lack of blinding
taining iron er vitamins time of re- tude where ap- at all levels.
in children and miner- ceiving the 3 trials con- Compari- propriate)
of preschool als on nutri- interven- ducted in son: no in-

and school malaria-en- tervention, IDA (defined by
tion, health tion with
age demic areas placebo or the presence of
and develop- MNP
usual sup- anaemia plus ID,
ment among
Anaemia plementa- diagnosed with
children at
prevalence: tion an indicator of
preschool (24
range = 7.3% iron status as se-
to 59 months)
to 92% among lected by trialists)
and school (5
the 9 trials re-
to 12 years) ID (defined by us-
porting these
age ing ferritin con-
data that did
not exclude centrations < 15
μg/L)
69
(Review)
participants Adverse effects
with anaemia (any, as defined
Library
Cochrane
by trialists)
Diarrhoea (3
liquid stools or
more per day)
Adjustments: not
Better health.
Informed decisions.
Trusted evidence.
reported
Eichler 2019 January 24 stud- To assess the RCTs Children Low- and mid- Inter- Hb (g/dL; conver- GRADE: Hb = very low,
2018 ies (9367 impact of MN (aged 5 to dle-income vention: sion to g/L with anaemia = very low, IDA =
Health ef- children fortified dairy Clus- 12 years) countries central- factor 10) very low, ID = very low, ad-
fects of mi- and ado- products and ter-RCTs and ado- ly-processed verse events = low
cronutri- lescents) cereal food on lescents Anaemia fortified Anaemia rate (<
ent fortified the health of (aged and malaria dairy prod- 11.5 g/dL (5 to 11 Cochrane RoB 1 tool for
dairy prod- children and 12 to 15 prevalence: ucts and for- years of age)); < RCTs. Only 4 of 24 studies
ucts and ce- adolescents years) of not reported tified cere- 12.0 g/dL (12 to were judged as having a low
real food for (aged 5 to 15 both sexes als, using 15 years of age)) risk of bias in at least 5 of 6
children and years) com- and from any fortifi- assessed domains.
adolescents: IDA
pared with all risk cation strat-
A systematic non-fortified groups. egy ID (ferritin level)
review food Stud-
ies with Compari- Adverse events
mixed son: non-
popu- fortified Adjustments: not
lation food reported
groups
were in-
cluded on-
ly if the
majori-

ty of par-
ticipants
were with-
in the age
range of 5
to 15 years
Fe: ferrum (iron); Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; MMN: multiple micronutrient; MN: micronutrient; MNP: micronutrient powders; RCT:
randomised controlled trial; WHO: World Health Organization.
70
(Review)
Table 5. Characteristics of included systematic reviews: adolescent children (aged 11 to 18 years)
search of includ- tion/objec- signs in- pants anaemia tion and comes (defin- vant outcomes
Library
Cochrane
ed trials tive cluded and malaria comparison ition used in
(number prevalence the review, Method used to assess risk of
of partic- adjusted for bias and summary
ipants in- smoking and
cluded) altitude)
Better health.
Informed decisions.
Trusted evidence.
Supplementation
Fernán- February 25 trials To assess the RCTs Menstruat- LMIC (15 tri- Interven- Hb (g/L) GRADE: intermittent iron sup-
dez-Gaxio- 2018 (10,996 effects of in- ing women, als) tion: in- plementation versus no supple-
la 2019 women) termittent Qua- that is termittent Anaemia (Hb mentation or placebo:
oral iron sup- si-RCTs women Europe (1 tri- dosage of concentration
Intermit- plementa- beyond al) iron alone below a cut- Hb = moderate, anaemia = low
tent iron Clus- off defined
tion, alone or menarche or with oth-
supple- ter-RCTs Latin America by trialists, IDA = low, ID = low, any adverse
in combina- and prior to er vitamins
menta- (4 trials) adjusted by side effects = moderate; in-
tion with oth- menopause and miner-
tion for altitude and termittent iron supplementa-
er nutrients, who are not Africa (5 trials) als
reducing smoking as tion versus daily iron: Hb = low,
on anaemia pregnant
anaemia Compari- appropriate) anaemia = moderate, IDA = no
and its as- or lactat- Asia (15 trials)
and its son: place- trials, ID = very low, any adverse
sociated im- ing or have
associ- Malaria: 5 tri- bo or no IDA (de- side effects = low
pairments in any condi-
ated im- als conducted interven- fined by the
menstruating tion that im- Cochrane RoB 1 tool
pairments in endemic ar- tion or the presence of
women, com- pedes the
in ado- eas same sup- anaemia plus
pared with no presence of Overall, most trials (23/25) were
lescent plements ID diagnosed
intervention, menstrual considered to be at high risk of
and adult Anaemia provided on with an indi-
a placebo or periods, re- bias due to lack of description
men- prevalence: a daily basis cator of iron
daily supple- gardless of of methods used for randomi-
struating 1 trial preva- status select-
mentation their base- sation and allocation conceal-
women lent, but per- ed by trialists)
line iron sta- ment and lack of blinding
tus/anaemia centage not
reported ID (defined by
status, eth-

trialists using
nicity, coun- indicators of
try of res- iron
idence or status such as
level of en- ferritin
durance. or transferrin)
(> 60% of Any adverse
the included side effects
trials includ- (e.g. nausea,
ed women vomiting,
under 18 constipation,
years) gastrointesti-
71
(Review)
Table 5. Characteristics of included systematic reviews: adolescent children (aged 11 to 18 years) (Continued)
nal discom-
fort, as de-
Library
Cochrane
fined by the
trialists)
Adjustments:
not reported
Neuberger MEDLINE 35 trials To evaluate RCTs Children Areas that Interven- Hb (g/dL) GRADE: not assessed
Better health.
Informed decisions.
Trusted evidence.
2016 (August (31,955 the effects (less than are malar- tion: iron Anaemia as
2015); children) and safety of Clus- 18 years of ia-endemic, supplemen- defined in The quality of studies was as-
Oral iron Other iron supple- ter-RCTs age), with and where tation, with trial Adjust- sessed by the Cochrane RoB 1
supple- databases mentation, or without children may or without ments: not re- tool; subgroup analyses per-
ments for (February with or with- anaemia, benefit from folic acid or ported formed. Publication bias as-
children 2015) out folic acid, and iron treat- antimalarial sessed by funnel plots. Around
in malar- in children liv- with or ment; the treatment 57% of studies were at low risk
ia-endem- ing in areas without baseline rate of bias related to allocation
ic areas with hyperen- malaria of malaria Compari- concealment, 74.5% of studies
demic or or para- parasitaemia son: place- to random sequence genera-
holoendemic sitaemia (reported in bo or no tion, and 77.1% to blinding.
malaria trans- 11 of 19 trials) treatment
mission ranged from or anti-
0% to 70% malarial
of children treatment
(mean 45%) (only when
the inter-
Anaemia vention is
prevalence: iron plus
not reported antimalari-
al)
Salam December 31 trials To ascertain RCTs Adolescent MN supple- Interven- Hb (g/L) GRADE: MN supplementation:
2016 2014 (MN sup- the effective- population mentation: tions: inter- anaemia = moderate; nutrition
plementa- ness of inter- Qua- (11 to 19 23/31 trials ventions to Anaemia (as in pregnancy: anaemia = low,

Interven- tion) ventions to si-RCTs years old) conducted in promote defined by tri- other outcomes = not assessed
tions to promote nu- Low-in- LMICs nutrition al authors)
improve 10 trials CBA trials Cochrane RoB 1 tool, but only
trition among come, preg- Nutrition in among ado-
adoles- (nutrition IDA GRADE is reported
adolescents nant adoles- pregnancy: lescent (e.g.
cent nu- in preg- comprising cents (13 to prenatal clin- micronutri- Adjustments:
trition: a nant ado- of MN supple- 20 years old) ics in urban ent supple- not reported
systemat- lescents) mentation, areas in Chile, mentation,
ic review nutrition in- (only data Ecuador, USA, nutrition in
and meta- terventions for adoles- Canada pregnancy)
analysis for pregnant cent popu-
adolescents, lation was Anaemia Compari-
and interven- extracted) and malaria son: control
72
(Review)
Table 5. Characteristics of included systematic reviews: adolescent children (aged 11 to 18 years) (Continued)
tions to pre- prevalence: (not speci-
vent obesity not reported fied)
Library
Cochrane
Salam February 10 stud- To assess the RCTs Adolescents School set- Interven- Anaemia; ad- GRADE: anaemia = low
2020 2019 ies (10,802 impact of pre- aged 10 to ting in LMICs: tion: MN justment: not
adoles- ventive nu- Clus- 19 years China, India, supplemen- reported Study quality assessed by
Effects of cents) trition inter- ter-RCTs Sri Lanka, tation/forti- Cochrane RoB 1 tool for RCTs
preven- ventions on Bangladesh, fication and EPOC risk of bias tool for
tive nutri- Qua- non-randomised studies. The
health and Indonesia
Better health.
Informed decisions.
Trusted evidence.
tion inter- si-RCTs Compari- included studies were judged to
nutritional
ventions status of ado- Anaemia son: place- be at unclear risk of bias due to
CBA
among lescents aged and malaria bo/no sup- insufficient information regard-
adoles- 10 to 19 years ITS prevalence: plementa- ing sequence generation, allo-
cents on in LMICs not reported tion/no for- cation concealment, and selec-
health and tification tive reporting.
nutrition-
al status in
low- and
middle-in-
come
countries
CBA: controlled before-and-after trials; EPOC: Effective Practice and Organisation of Care; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; ITS: interrupted
time series; LMICs: low- and middle-income countries; MN: micronutrient; RCTs: randomised controlled trials.
Table 6. Characteristics of included systematic reviews: non-pregnant women of reproductive age (aged 19 to 49 years)
Review Date of Number Review Trial de- Partici- Setting, Interven- Relevant out- GRADE assessment of relevant
search of includ- ques- signs in- pants anaemia tion and comes (def- outcomes
ed trials tion/objec- cluded and malaria compari- inition used
(number tive prevalence son in the review, Method used to assess risk of
of partic- adjusted for bias and summary

ipants in- smoking and
cluded) altitude)
Supplementation
Abe 2016 Septem- 2 trials (52 To evaluate RCTs Non- Brazil, USA Interven- Anaemia (ma- GRADE: intended but not as-
ber 2015 women) the effects pregnant tion: MMN ternal haemo- sessed due to lack of outcomes
Supplemen- of MMN sup- mothers Anaemia supple- globin level < 12
tation with plemen- who ex- and malaria ments of g/dL or mater- Cochrane RoB 1 tool. Most do-
multiple tation in clusively prevalence: 3 or more nal serum fer- mains were rated as unclear
micronu- breastfeed- fed breast not reported micronu- ritin < 15 μg/L) overall due to lack of information
trients for ing mothers milk or trients in both trial reports
73
(Review)
Table 6. Characteristics of included systematic reviews: non-pregnant women of reproductive age (aged 19 to 49 years) (Continued)
breastfeed- on maternal practiced Compari- Adverse effects
ing women and infant mixed son: place-
Adjustments:
Library
Cochrane
for improv- outcomes feeding bo, no
ing out- (breast supple- not reported
comes for milk and mentation
the mother formu- or supple-
and baby la). HIV- mentation
positive with 2 or
women fewer mi-
Better health.
Informed decisions.
Trusted evidence.
were ex- cronutri-
cluded ents, irre-
spective of
dosage of
micronu-
trient
Houston October 18 trials To identify RCTs Adults (≥ North Amer- Interven- Hb (g/L) GRADE: not assessed
2018 2016 (from 20 the effects 18 years) ica (8 trials), tion: oral,
reports) of iron ther- who were Europe (7 tri- IM or IV Anaemia (Hb Cochrane RoB 1 tool. Overall, 1
Efficacy of (1170 par- apy on fa- iron de- als), Australia iron sup- < 130 g/L for trial was rated at low risk of bias
iron supple- ticipants) tigue and ficient (2 trials), Asia plementa- males, < 120 g/L while the remaining trials were
mentation physical ca- but non- (1 trial) tion for females) rated at unclear risk of bias. 13
on fatigue pacity in ID- anaemic; trials were adequate for perfor-
and physi- Anaemia Compari- Adjustments: mance bias and 10 for detection
NA adults
cal capac- 15 trials and malaria son: place- not reported bias. Randomisation was ade-
ity in non- includ- prevalence: bo or ac- quate in 6 trials and allocation
anaemic ed only not reported tive thera- concealment in 5 trials.
iron-defi- women, py
cient adults: with >
a systemat- 60% with-
ic review of in this age
randomised group
controlled

trials
Lassi 2020 May 2019 45 trials To synthe- RCTs Women of Low- and mid- Interven- Anaemia GRADE: anaemia - RCTs = very
(10 trials sise the cur- reproduc- dle- income tion: peri- low, anaemia - weekly supple-
Effects of for iron rent evi- Quasi-ex- tive age countries: concep- Adjustments: mentation = very low, anaemia -
preconcep- supple- dence on perimen- Bangladesh (2 tional iron not reported daily supplementation = very low
tion care menta- the effec- tal trials), India folic acid
and peri- tion, in- tiveness of (2 trials), In- supple- Risk of bias assessment com-
conception Natural prised of Cochrane RoB 1 and
cluding preconcep- donesia (3 tri- mentation
interven- experi- EPOC criteria. Eight trials were
8955 par- tion care in- als), Nepal (1
tions on ma- ment Compari- assessed unclear or low risk of
ticipants; terventions trials), Mali (1
ternal nutri- data and relating to trials), Tanza- son: place- bias in selection bias and at-
74
tional status informa- the delayed nia (1 trials) bo trition bias. Two trials were as-
(Review)
and birth tion only age at first Anaemia sessed as high risk of bias in se-
outcomes extracted pregnancy; and malaria lection bias or attrition bias each.
Library
Cochrane
in low- and for those optimising prevalence:
middle-in- trials) inter-preg- not reported
come coun- nancy inter-
tries: a sys- vals
tematic re-
view
Better health.
Informed decisions.
Trusted evidence.
Low 2016 November 67 tri- To estab- RCTs Menstru- Trials were Interven- Hb (g/L) GRADE: Hb = high, anaemia =
2015 als (8506 lish the evi- ating conducted tion: daily moderate, IDA = not assessed, ID
Daily iron women) dence for ef- Clus- women, in numerous oral iron Anaemia (Hb = moderate, any adverse side ef-
supplemen- fects of dai- ter-RCTs that is, countries of supple- concentrations fect = low
tation for ly supple- women differing cul- menta- below a cut-off
improving Qua- defined by trial Cochrane RoB 1 tool. Overall,
mentation beyond tural and eco- tion with
anaemia, si-RCTs authors) trial methods were not well de-
with iron menar- nomic back- or without
iron status on anaemia che and grounds a co-inter- scribed. 14 trials used adequate
and health IDA (defined by methods for random sequence
and iron sta- prior to vention
in men- Malaria: 1 trial the presence of generation and 15 for allocation
tus, as well menopause (folic acid
struating conducted in anaemia plus concealment. Blinding of partici-
as on phys- who were or vitamin
women endemic area iron deficiency, pants was not attempted in 8 tri-
ical, psy- not preg- C)
diagnosed with als (unlikely to impact on labora-
chological nant or
Anaemia Compar- an indicator of tory outcomes). Overall, only 10
and neu- lactating
prevalence: ison: no iron status se- trials were assessed as being at
rocognitive or had any
not reported supple- lected by trial- low overall risk of bias.
health, in condition
mental ists)
menstruat- that im-
ing women peded the iron
Iron deficiency
presence (as measured
of men- by trial authors
strual pe- using indicators
riods of iron status
such as ferritin
or transferrin)

Any adverse
side effects (as
measured by
trial authors
such as abdom-
inal pain, vom-
iting, nausea,
heartburn, di-
arrhoea, consti-
pation)
75
(Review)
Adjustments:
not reported
Library
Cochrane
Sultan 2019 November 15 studies To compare RCTs Women India (4 trials), Interven- Hb (g/dL) GRADE: not assessed
2017 (2182 par- oral versus with a Greece (2 trition: IV
Oral versus ticipants) IV iron ther- postdeliv- als), USA (2 iron Treatment-re- Cochrane RoB 1 tool. Eight tri-
intravenous apy to treat ery Hb lev- trials), Nor- lated side ef- als were low risk for random se-
iron therapy postpartum el of < 12 way, Roma- Compari- fects quence generation and 7 unclear.
for postpar- anaemia g/dL nia, Egypt, son: oral Allocation concealment was only
Better health.
Informed decisions.
Trusted evidence.
tum anemia: iron Adjustments: adequate in 6 trials. Performance
UK, Spain,
a systematic not reported bias was high risk in 14 trials and
Denmark,
review and Pakistan unclear in 1. Detection bias was
meta-analy- high risk in 6 trials, low risk in 7
sis Anaemia and unclear in 1 trial.
and malaria
prevalence:
not reported
EPOC: Effective Practice and Organisation of Care; Hb: haemoglobin; IDA: iron deficiency anaemia; IDNA: iron-deficient non-anaemic; IM: intramuscular; IV: intravenous; MMN:
multiple micronutrient; RCTs: randomised controlled trials.
Table 7. Characteristics of included systematic reviews: pregnant women (aged 15 to 49 years)

search of includ- tion/objec- signs in- pants anaemia tion and comes (defini- vant outcomes
ed trials tive cluded and malaria comparison tion used in the
(number prevalence review, adjusted Method used to assess risk of
of partic- for smoking and bias and summary
ipants in- altitude)
cluded)
Supplementation

Abu February 4 tri- To evaluate RCTs Pregnant Italy (3 tri- Interven- Change in Hb lev- GRADE: Hb levels = low, gas-
Hashim 2017 als (600 the efficacy women als), Egypt tion: oral el (g/dL) after at trointestinal side effects = mod-
2017 women) of daily oral with IDA (1 trial) bovine least 4 weeks of erate
bovine lacto- (Hb < 11 g/ lactoferrin treatment
Lactofer- ferrin ver- dL) Anaemia Rates of gastroin- Cochrane RoB 1 tool. Risk of
rin or fer- sus daily oral and malaria Compari- testinal side ef- bias was mostly unclear for the
rous salts ferrous iron prevalence: son: oral fer- fects during the important domains of random
for iron preparations not reported rous iron treatment peri- sequence generation, alloca-
deficiency for treatment prepara- od (epigastric dis- tion concealment and blinding.
anemia in of IDA during tions comfort, nausea, Other domains were at low risk
pregnan- pregnancy vomiting, diar- of bias
76
(Review)
Table 7. Characteristics of included systematic reviews: pregnant women (aged 15 to 49 years) (Continued)
cy: a meta- rhoea, constipa-
analysis of tion, abdominal
Library
Cochrane
random- colicky pain and
ized trials dark stools)
Adjustments: not
reported
Bhutta Septem- 7 trials To compare RCTs Healthy All trials Interven- Maternal Hb GRADE: Hb = low, anaemia =
Better health.
Informed decisions.
Trusted evidence.
2012 ber 2011 (18,595 the effects of pregnant were from tion: MMN moderate
pregnant MMN supple- Clus- women low or mid- supplemen- Maternal
Is it time women) ments dur- ter-RCTs dle-income tation anaemia in the Cochrane RoB 1 tool. 6 trials as-
to replace ing pregnan- settings third trimester sessed at low risk of bias and
iron folate cy versus iron Compari- 1 trial assessed at high risk of
supple- Anaemia son: iron fo- Adjustments: not bias
folate for the
ments in and malaria late supple- reported
prevention
pregnancy of maternal prevalence: mentation
with mul- anaemia not reported
tiple mi-
cronutri-
ents?
Buppasiri Septem- 25 trials, To determine RCTs Pregnant Argentina, Interven- Maternal GRADE: not assessed for rele-
2015 ber 2014 of which, the effect of women Australia, tion: calci- anaemia (as de- vant outcomes
23 con- calcium sup- who re- Columbia, um supple- fined by the trial
Calcium tributed plementa- ceived any Ecuador, mentation authors) Cochrane RoB 1 tool. Most of
supple- data tion on ma- calcium Egypt, during preg- the trials (17 out of 25) were rat-
menta- (18,578 ternal, fetal supple- Gambia, nancy Adjustments: not ed at low risk of bias for both
tion (oth- pregnant and neona- menta- Guatemala, reported sequence generation and allo-
er than for women) tal outcomes tion com- Hong Kong, Compari- cation concealment
preventing (other than pared with India, Iran, son: place-
or treating for preventing placebo or Mexico, bo or no
hyperten- or treating hy- no treat- South treatment
sion) for pertension), ment Africa, USA

improving including the and Vietnam
pregnancy occurrence of
and infant side effects Anaemia
outcomes and malaria
prevalence:
not reported
Daru 2016 January 23 tri- To assess RCTs Pregnant Not report- Interven- Hb GRADE: not assessed
2015 als (3525 the effect on women at ed tion: iron
System- women) serum ferritin any gesta- supplemen- Adjustments: not Jadad method used to as-
atic re- (iron stores) tion with Anaemia tation (oral, reported sess trial quality (a score of > 3
view of and Hb (oxy- NAID or and malaria including equated to good quality). 12 tri-
77
(Review)
random- gen-carrying IDA, or prevalence: fortified wa- als were of high quality and 11
ized tri- capacity) fol- both not reported ter, of low quality
Library
Cochrane
als of the lowing iron
effect of supplementa- intravenous
iron sup- tion in preg- or intramus-
plemen- nant women cular)
tation on with anaemia
Compari-
iron stores and NAID
son: place-
and oxy-
Better health.
Informed decisions.
Trusted evidence.
bo, or oral
gen carry-
or intramus-
ing capac-
cular iron
ity in preg-
prepara-
nancy
tions
Das 2018 May 2018 3 RCTs To assess RCTs Women Stable com- Interven- Hb GRADE: anaemia = moderate
and 1 clus- the effects of with sin- munity tion: LNS
Lipid- ter-RCT LNS for ma- Clus- gleton settings: Anaemia (Hb less Cochrane RoB 1 tool
based nu- (8018 ternal, birth ter-RCTs pregnancy Ghana, Compari- than 110 g/L)
trient sup- pregnant and infant of any age Malawi, son: no in-
plements tervention, Adverse effects
women) outcomes and parity Burki-
for mater- in pregnant na Faso, placebo,
Adjustments: not
nal, birth, women Bangladesh IFA, MMNs
reported
and infant Anaemia or nutri-
develop- and malaria tional coun-
mental prevalence: selling
outcomes not reported
De-Regil August 5 trials To examine RCTs Pregnant Settings: 4 Interven- Maternal GRADE: not assessed for rele-
2015 2015 (7391 whether peri- women ≤ trials from 9 tion: peri- anaemia at or vant outcomes
women) conception- 12 weeks' high-income conception- near term (Hb
Effects al folate sup- gestation countries, 1 al folate or < 110 g/L at 34 Cochrane RoB 1 tool. Trials
and safety plementation at the time trial from 1 folic acid weeks' gestation were rated at unclear or low
of pericon- reduces the of inter- lower- mid- supplemen- or more) risk of bias for allocation con-

ception- risk of neur- vention dle-income tation alone cealment and blinding
al oral fo- al tube and country or in combi- Adjustments: not
late sup- other congen- nation with reported
plemen- ital anomalies Anaemia other vita-
tation for (including and malaria mins or min-
preventing cleft palate) prevalence: erals
birth de- without caus- not reported
fects ing adverse Compar-
outcomes in ison: no
mothers or treatment
babies or placebo
or other mi-
78
(Review)
cronutrients
without fo-
Library
Cochrane
late
Govin- October 11 trials To study ben- RCTs Pregnant India (7 tri- Interven- Hb in response to GRADE: not assessed
dappagari 2017 (1190 par- efits of IV iron women als), France tion: IV iron treatment
2019 ticipants) over oral iron with IDA (1 trial), Cochrane RoB 1 tool. The do-
for treatment Turkey (1 tri- Compar- Hb after 4 weeks mains random sequence gen-
Treatment of anaemia in al), Egypt (1 ison: oral of treatment eration, incomplete outcome
Better health.
Informed decisions.
Trusted evidence.
of iron de- pregnancy trial), mul- iron data, selective reporting and
ficiency Adverse effects other bias were adequate in all
ti-country (1
anemia in trial) trials. All trials were high risk
Adjustments: not
pregnan- of bias for performance and
reported
cy with in- Anaemia detection bias due to lack of
travenous and malaria blinding. Allocation conceal-
versus oral prevalence: ment was unclear in most trials.
iron: sys- not reported
temat-
ic review
and meta-
analysis
Haider December 14 trials To evaluate RCTs Pregnant All trials Interven- Maternal GRADE: anaemia = high
2011 2009 (17 re- the evidence women were from tion: MMN anaemia in the
ports) of the impact Clus- (any ges- low-income supple- third trimester Cochrane RoB 1 tool. Overall, 9
Effect of of MMN sup- ter-RCTs tation) or mid- mentation trials were of high quality and
multiple plements dur- dle-income (at least 5 Adjustments: not 5 moderate. Some of the trials
micronu- ing pregnan- settings MMNs, in- reported had limitations based on trial
trient sup- cy, in com- cluding the design and execution such as
plementa- parison with Anaemia UNIMMAP large losses to follow-up, insuf-
tion dur- standard iron- and malaria formulation ficient power to detect differ-
ing preg- folate sup- prevalence: or those ences in small-for-gestational
nancy on plements, on not reported with compa- age and mortality, and missing
maternal specific ma- rable com- compliance data.

and birth ternal and position)
outcomes pregnancy
outcomes Compari-
of relevance son: mater-
to the Lives nal iron-fo-
Saved Tool late supple-
mentation
Haider May 2012 48 trials To summarise RCTs Pregnant 27 trials Interven- Mean Hb concen- GRADE: not assessed
2013 (17,793 evidence women conducted tion: dai- tration (g/L)
women) on the as- Clus- in high-in- ly oral iron Risk of bias tool not stated, but
sociations ter-RCTs come coun- or iron and trial quality was assessed us-
79
(Review)
Anaemia, 44 co- of maternal Cohort tri- tries (4861 folic acid Anaemia (Hb < ing the following domains: ran-
prenatal hort trials anaemia and als women), 21 (both sup- 110 g/L) domisation technique, conceal-
Library
Cochrane
iron use, (1,851,682 prenatal iron in low- or plementa- ment of allocation, blinding,
and risk women) use with ma- Data only middle-in- tion and for- IDA (Hb < 110 g/ and loss to follow-up. 18 trials
of adverse ternal haema- extracted come coun- tification) L and serum fer- deemed to be of high quality
pregnancy tological and for RCTs tries (12,932 ritin < 12 µg/L) (adequate for randomisation
outcomes: adverse preg- women) Compari- and allocation concealment
son: place- ID (defined as
systemat- nancy out- plus either blinding or loss to
Malaria en- bo, no iron, serum ferritin <
ic review comes; and to follow-up under 20%)
Better health.
Informed decisions.
Trusted evidence.
demicity: or no iron 12 μg/L) in the
and meta- evaluate po-
endemic in and folic second or third
analysis tential expo-
7 trials, non- acid trimester or at
sure-response
endemic in delivery and in
relations of
29 trials the postpartum
dose of iron,
period
duration of
Baseline
use, and Hb Adjustments: not
anaemia:
concentra- reported
anaemic in
tion in pre-
7 trials, non-
natal period
anaemic in
with pregnan-
26 trials
cy outcomes
Imdad June 2011 30 trials To assess the RCTs Pregnant High-in- Interven- Maternal GRADE: anaemia at term =
2012 impact of rou- women come and tion: pre- anaemia at term moderate
tine iron sup- Clus- low-income natal iron (Hb < 110 g/L)
Routine plementation ter-RCTs countries or iron plus Assessed trial limitations using
iron/fo- on maternal folic acid Severe anaemia GRADE. Limitations for trials re-
late sup- Qua- Anaemia (at term or any porting anaemia at term: tri-
anaemia and
plementa- si-RCTs and malaria Compari- time during sec- als with unclear or inadequate
perinatal out-
tion dur- comes prevalence: son: place- ond or third sequence generation and high
ing preg- not reported bo or no in- trimester) loss to follow-up
nancy: ef- tervention
fect on Maternal IDA (Hb
maternal < 110 g/L)

anaemia
Adjustments: not
and birth
reported
outcomes
Keats 2019 February 21 trials To evaluate RCTs Pregnant All trials, ex- Intervention Maternal GRADE: not assessed for rele-
2018 (142,496 the benefits women at cept 1, were and com- anaemia (third vant outcomes
Multi- women) of oral MMN Clus- any length from low- parison: trimester (Hb <
ple-mi- supplemen- ter-RCTs of gesta- and mid- 110 g/L) Cochrane RoB 1 tool. The risk
cronutri- tation during tion at the dle-income • MMN of bias was generally low with
ent sup- pregnancy on time of en- settings with iron Side-effects of at least 50% of the judgements
plemen- maternal, fe- rolment in and folic MMN supple- at low risk of bias for 2 domains
tation for tal and infant the trial acid ver- ments (no data) (allocation
80
(Review)
women health out- Malaria: 5 sus con- Adjustments: not concealment and incomplete
during comes trials report- trol (iron reported outcome data) and at least 75%
Library
Cochrane
pregnancy ed malaria with or of the judgements at low risk
prophylaxis without of bias for the remaining 5 do-
folic acid) mains.
Anaemia • MMN
prevalence: with iron
not reported and folic
acid ver-
Better health.
Informed decisions.
Trusted evidence.
sus con-
trol
(placebo)
Lassi 2013 December 31 trials To assess RCTs Pregnant The major- Interven- Mean pre-deliv- GRADE: not assessed
2012 (17,771 the effective- women of ity of tri- tions: ery Hb
Folic acid women) ness of oral Clus- any age als were Cochrane RoB 1 tool. All includ-
supple- folic acid sup- ter-RCTs and parity conducted • folic acid Pre-delivery ed trials were conducted over
menta- plementa- in Europe, alone anaemia (< 10 g/ 30 to 45 years ago. The review-
tion dur- Qua- versus no dL, Hb or haema- ers found poor subjective and
tion alone or Africa and
ing preg- si-RCTs treat- tocrit below 30%) objective compliance with ran-
with other mi- Asia. 1 tri-
nancy for cronutrients al was con- ment/place- dom allocation, adequate con-
maternal versus no folic ducted in bo (no Adjustments: not cealment and blinding.
health and acid (placebo South Amer- folic acid) reported
pregnancy or same mi- ica, 1 in Aus- • folic acid
outcomes cronutrients tralia and + iron
but no folic 1 in New versus
acid) during Zealand iron (no
pregnancy on folic acid)
haematolog- Anaemia • folic acid
ical and bio- and malaria + oth-
chemical pa- prevalence: er vita-
rameters dur- not reported mins and
ing pregnancy minerals

and on preg- versus
nancy out- other vit-
comes amins
and min-
erals (but
no folic
acid)
Compari-
son: place-
bo or same
micronutri-
81
(Review)
ents but no
folic acid
Library
Cochrane
McCauley March 19 tri- To review the RCTs Pregnant Africa (7 tri- Interven- Maternal GRADE: maternal anaemia =
2015 2015 als (over effects of sup- women als), Indone- tion: vita- anaemia (Hb < moderate
310,000 plementation Clus- sia (6 trials), min A (or 11.0 g/dL)
Vitamin women) of vitamin A, ter-RCTs Bangladesh one of its Cochrane RoB 1 tool. One-third
A supple- or one of its (2 trials), derivatives) Neonatal of the trials were at low risk of
menta- Qua- anaemia (as de- bias for random sequence gen-
derivatives, Nepal (1 tri- supple-
Better health.
Informed decisions.
Trusted evidence.
tion dur- si-RCTs fined by investi- eration and half of the trials
during preg- al), China (1 mentation,
ing pregnancy, alone trial), India alone or gator) were adequate for allocation
nancy for or in combi- (1 trial) concealment. The risk of per-
maternal in combi- Adjustments: not formance bias was low in 80%
nation with
and new- Anaemia nation with reported of the trials, but only 25% of the
other vita-
born out- mins and mi- and malaria other sup- trials for detection bias. Selec-
comes cronutrients, prevalence: plements tive reporting bias was unclear
on maternal malaria in 18 of the 19 trials.
prevalence Compari-
and newborn
reported in son: place-
clinical out-
3 trials bo or no
comes
treatment
Peña- February 61 trials To assess the RCTs Pregnant Europe Interven- Maternal Hb con- GRADE: any supplements con-
Rosas 2015 (44 with effects of dai- women of (24 trials), tion: any centration at or taining iron versus same sup-
2015b 43,274 ly oral iron Clus- any gesta- Americas supple- near term (in g/L, plements without iron or no
women supplements ter-RCTs tional age (11 trials), ments con- at 34 weeks’ ges- treatment or placebo (no iron
Daily oral contribut- for pregnant and parity Africa (4 tri- taining iron tation or more) or placebo): maternal anaemia
iron sup- Qua-
ing data) women, ei- als), Iran (4 at term = low, maternal ID at
plementa- si-RCTs Compari- Maternal Hb con-
ther alone or trials), Hong term = low, maternal severe
tion dur- in conjunc- Kong (1 tri- son: same centration within anaemia at any time during
ing preg- tion with folic al), China (4 supple- 6 weeks postpar- second and third trimester =
nancy acid, or with trials), Aus- ments with- tum very low, side effects = very low;
other vita- tralia (3 tri- out iron or (in g/L) any supplements containing
mins and min- als), Asia (8 no treat- iron and folic acid versus same

ment or Maternal
erals as a pub- trials) supplements without iron nor
placebo anaemia at term
lic health in- folic acid (no iron nor folic acid
Anaemia (no iron or (Hb < 110 g/L at
tervention or placebo): maternal anaemia
and malar- placebo) 37 weeks’ gesta-
in antenatal at term = moderate, maternal
ia preva- tion or more)
care ID at term = low, maternal se-
lence: 23 tri- vere anaemia at any time dur-
Maternal
als conducting second and third trimester
anaemia at or
ed in malar- = very low, side effects = mod-
near term (Hb
ia-risk areas, erate, other outcomes = not as-
< 110 g/L at 34
anaemia sessed
weeks’ gestation
prevalence
or more)
unclear
82
(Review)
Moderate Cochrane RoB 1 tool. Only 25
anaemia at post- trials were at low risk of bias for
Library
Cochrane
partum (Hb be- random sequence generation
tween 80 and 109 and 22 for allocation conceal-
g/L) ment. Blinding was adequate in
about half of the trials. Almost
Maternal IDA at all trials were of unclear risk of
term (as defined bias for selective reporting
by trialists at 37
Better health.
Informed decisions.
Trusted evidence.
weeks’ gestation
or more)
Maternal IDA at
or near term (Hb
< 110 g/L and
at least 1 addi-
tional laborato-
ry indicator at 34
weeks’ gestation
or more)
Maternal ID at
term (as defined
by trialists, based
on any indicator
of iron status at
37 weeks’ gesta-
tion or more)
Maternal ID at or
near term (as
defined by tri-
alists, based on
any indicator of

iron status at 34
weeks’s gestation
or more)
Severe anaemia
at any time dur-
ing second or
third trimesters
(Hb < 70 g/L)
Maternal severe
anaemia at or
near term (Hb
83
(Review)
< 70 g/ L at 34
weeks’ gestation
Library
Cochrane
or more)
Severe anaemia
postpartum (Hb <
80 g/L)
Side effects
Better health.
Informed decisions.
Trusted evidence.
(any reported
throughout inter-
vention period)
Diarrhoea (as de-

fined by trialists)
Constipation (as
defined by trial-
ists)
Vomiting (as de-

fined by trialists)
Adjustments: not
reported
Peña- July 2015 21 tri- To assess the RCTs Pregnant Argenti- Interven- Maternal Hb con- GRADE: any intermittent iron
Rosas als (5490 benefits and women na (1 trial), tion: oral centration at or regimen (with or without oth-
2015a women) harms of in- Qua- Bangladesh supple- near term (g/L, at er vitamins and minerals) ver-
termittent si-RCTs (1 trial), Chi- ments of 34 weeks’ gesta- sus daily regimen (with same
Intermit- supplementa- na (1 trial), iron, or iron tion or more) vitamins and minerals): ma-
tent oral Clus-
tion with iron Guatemala + folic acid, Maternal ternal anaemia at term = very
iron sup- ter-RCTs
alone or in (2 trials), In- or iron + anaemia at term low, maternal severe anaemia
plementa- combination dia (4 tri- vitamins (Hb < 110 g/L at at any time during second
tion dur- with folic acid als), Indone- and miner- 37 weeks' gesta- and third trimester = very low,

ing preg- or other vita- sia (2 trials), als, given tion or more) maternal IDA at term = very
nancy mins and min- Iran (5 tri- as a public Maternal low, side effects (any reported
erals to preg- als), Malawi health strat- anaemia at or throughout the intervention
nant women (1 trial), egy on an near term (Hb period) = very low, other out-
on neonatal Malaysia (1 intermittent < 110 g/L at 34 comes = not assessed
and pregnan- trial), Mexi- basis weeks’ gestation
cy outcomes co (3 trials), or more) Cochrane RoB 1 tool. About half
Pakistan Compari- Moderate of the trials were at low risk of
(2 trials), son: place- anaemia at any bias for random sequence gen-
South Korea bo or no time during sec- eration, but 5 trials were at high
(1 trial), Sri supplemen- ond and third risk of bias. Allocation conceal-
Lanka (1 tri- tation, or trimester (Hb be- ment was adequate in only 3
84
(Review)
al),Thailand the same tween 70 and 99 trials and at high risk in 9 trials.
(1 trial), and supple- g/L) All trials, except 1, were at high
Library
Cochrane
Vietnam (1 ments pro- Maternal IDA at risk of performance bias. Con-
trial) vided daily term (Hb < 110 g/ trary, all trials, except 1, were at
L and at least 1 low risk of detection bias.
Malaria additional labo-
prevalence: ratory indicator
all countries at 37 weeks’ ges-
with some tation or more)
Better health.
Informed decisions.
Trusted evidence.
malaria risk Maternal IDA at
term or near term
Anaemia
(Hb < 110 g/L and
prevalence:
at least 1 addi-
not reported
tional laborato-
ry indicator at 34
weeks’ gestation
or more)
Maternal ID at
or near term (as
defined by tri-
alists, based on
any indicator of
iron status at 34
weeks’ gestation
or more)
Severe anaemia
at any time dur-
ing second or
third trimesters
(Hb < 70 g/L)
Severe anaemia
at or near term
(Hb < 70 g/L at 34
weeks’ gestation

or more)
Severe anaemia
at term (Hb < 70
g/L at 37 weeks’
gestation or
more)
Severe anaemia
at postpartum
(Hb < 80 g/L)
Side effects
(any reported
throughout the
85
(Review)
intervention peri-
od)
Library
Cochrane
Diarrhoea (as de-
fined by trialists)
Constipation (as
defined by trial-
ists)
Vomiting (as de-
fined by trialists)
Better health.
Informed decisions.
Trusted evidence.
Adjustments:
some trials ad-
justed for altitude
Qassim June 2016 47 studies To evaluate RCTs Pregnant Any coun- Interven- Hb (g/L); adjust- GRADE: not assessed
2018 (2635 in the efficacy women tries: In- tion: IV IPM, ment: not report-
IS group, and safety of Qua- with IDA dia, USA, IS and FCM ed Study quality assessed by
Safety and 276 in FCM IV IPM, IS and si-RCTs Pakistan Cochrane RoB 1 tool for RCT
efficacy group, FCM in the and several Compar- studies and RoBANS for non-
of intra- Obser- ison: any randomised studies. One-quar-
164 in IPM management countries
venous vational other com- ter of the included trials had
group) of antenatal
iron poly- studies Anaemia parator high risk of bias in at least one
IDA
maltose, and malaria domain, whereas 12 of 26 ob-
iron su- prevalence: servational studies had high
crose and not reported risk of bias in at least one do-
ferric car- main.
boxymal-
tose in
pregnan-
cy: a sys-
tematic
review
Qassim January 15 studies To compare RCTs Pregnant Any country: Interven- Hb (g/L); adjust- GRADE: Hb = low
2019 2019 (1938 par- the effects women Singapore, tion: IV iron ment: not report-

ticipants) on perinatal who ini- France, therapy ed Cochrane RoB 1 tool used to
Intra- maternal and tially Turkey, Aus- assess risk of bias. All studies
venous or neonatal out- had low tralia, India, Compar- were at high risk of bias due to
oral iron comes of in- haemoglo- Thailand ison: oral lack of blinding participants or
for treat- travenous and bin levels and several iron study personnel.
ing iron oral iron ther- (< 110 g/L) countries
deficiency apy as first- or were at
anaemia line treatment high risk Anaemia
during of IDA in preg- of devel- and malaria
pregnan- nant women oping IDA prevalence:
cy: sys- not reported
temat-
86
(Review)
ic review
and meta-
Library
Cochrane
analysis
Radhika August 18 stud- To confirm RCTs Antenatal Developing Interven- Hb (g/L); adjust- GRADE: Hb = high in pregnant
2019 2011 to ies (1633 the safety and and post- countries tion: par- ment: not report- women, moderate in post-par-
March antenatal efficacy of partum enteral iron ed tum women
Parenteral 2018 women) intravenous women di- Anaemia (IV IS)
versus oral and 8 iron sucrose agnosed and malaria The quality of studies was as-
Better health.
Informed decisions.
Trusted evidence.
iron for studies compared to with IDA prevalence: Compar- sessed by Cochrane RoB 1
treatment (713 post- oral iron for not reported ison: oral tool; subgroups and sensitivi-
of iron de- partum treatment iron ty analyses performed. Publi-
ficiency women) of IDA in an- cation bias assessed by testing
anaemia tenatal and the intercept of Egger regres-
during post-partum sion. All studies had loss to fol-
pregnancy women low-up and dropout rates less
and post- than 20%.
partum: a
systematic
review
Reveiz June 2011 23 tri- To assess the RCTs Pregnant Not report- Interven- Hb GRADE: not assessed
2011 als (3198 effects of dif- women ed tions:
women) ferent treat- with a di- Anaemia Cochrane RoB 1 tool. Half of the
Treat- ments for agnosis of Anaemia • Oral iron trials were at low risk of bias
ments for and malaria • Oral iron Side effects for random sequence genera-
anaemia in anaemia
iron-de- pregnancy at- (Hb levels prevalence: plus ad- tion and about half of the trials
Nausea and vom-
ficiency tributed to < 11 g/dL, not reported juncts were at unclear risk of bias. Al-
iting
anaemia ID (defined or other • Intra- location concealment was rat-
in preg- as haemo- tests for muscular Constipation ed at low risk of bias in about
nancy globin < 11 anaemia iron one-third of the trials and two-
g/dL or oth- as de- Diarrhoea thirds were unclear. Blinding
• IV iron
er equivalent scribed by was rated at high risk of bias in
• Blood Adjustments: not more than half of the trials and
parameters) trialists)

transfu- reported only one-third were deemed to
on maternal attributed
sion be at low risk for performance
and neonatal to ID
morbidity and • Recombi- and detection bias
mortality nant ery-
thropoi-
etin
Compari-
son: place-
bo or no
interven-
tion or oth-
87
(Review)
er type of in-
tervention
Library
Cochrane
Rumbold 31 March 29 trials To identify RCTs All preg- High-in- Interven- Maternal Hb (no GRADE: not assessed for rele-
2015 2015 (24,300 all published nant come coun- tion: vita- data reported for vant outcomes
women) and unpub- Qua- women tries: Aus- min C sup- this outcome)
Vitamin lished ran- si-RCTs tralia, Cana- plementa- Cochrane RoB 1 tool. About
C supple- domised and da, the tion, alone Maternal two-thirds of trials were at
mentation quasi-ran- Nether- or in combi- anaemia (no data low risk of bias for random se-
Better health.
Informed decisions.
Trusted evidence.
in preg- domised con- lands, UK nation with reported for this quence generation, allocation
nancy trolled trials and USA other sepa- outcome) concealment and blinding of
investigating rate supple- participants and personnel.
Low- and Side effects
vitamin C sup- ments
plementation middle-in-
Adjustments: not
in pregnancy come coun- Compari-
reported
and to investi- tries: Brazil, son: place-
gate the ben- India, Iran, bo, no
efits and haz- Latvia, Mex- placebo or
ards of vita- ico, Pe- other sup-
min C supple- ru, South plements
mentation in Africa,
pregnancy Turkey,
Uganda,
Vietnam,
Venezuela
Anaemia
and malaria
prevalence:
not reported
Shi 2015 January 6 tri- To assess the RCTs Pregnant India (4 tri- Interven- Mean Hb concen- GRADE: not assessed
2014 als (576 efficacy and women di- als), not re- tion: IV IS tration (g/dL)
Intra- women) safety of IV IS agnosed ported (2 tri- Cochrane RoB 1 tool. 5 trials

venous in pregnancy with IDA als) Compar- Adverse events were deemed adequate for ran-
iron su- with IDA ison: oral dom sequence generation and
crose ver- Anaemia iron supple- Adjustments: not 3 for allocation concealment.
sus oral and malaria ment reported All trials were rated at high risk
iron in prevalence: of performance bias and 1 tri-
the treat- not reported al was rated at high risk of de-
ment of tection bias. The remaining tri-
pregnancy als were rated at unclear risk of
with iron bias
deficiency
anaemia:
88
(Review)
a system-
atic review
Library
Cochrane
Thorne- November 17 trials To consoli- RCTs Pregnant Low-mid- Interven- Mean Hb GRADE: Hb = moderate, mater-
Lyman 2010 and date women dle income tion: sup- nal anaemia = high, severe ma-
2012 June knowledge Clus- (anaemic countries: plementa- Maternal ternal anaemia = low
2011 about the ef- ter-RCTs or non- India, South tion with vi- anaemia (< 11 g/
Vitamin fects of sup- anaemic Africa, tamin A or dL) Trial bias was assessed by a
A and plementation women, Ghana, In- carotenoids slightly modified version of the
Better health.
Informed decisions.
Trusted evidence.
carotenoids Severe maternal CHERG’s GRADE tool.
on 3 trials donesia, (or both)
during anaemia (< 8.0 or Methodological quality was
multiple out- includ- Tanzania,
pregnan- Compari- 8.5 g/dL) deemed high in 10 trials, mod-
comes related HIV- Malawi,
cy and ed to mater- positive China, son: place- erate in three trials and low in
Adjustments: not
maternal, nal, perina- women) Nepal, and bo and mul- four trials
reported
neonatal and infant Bangladesh tivitamins
tal and in- health to in- alone
fant health form policy in Anaemia
outcomes: low-income and malaria
a system- countries and prevalence:
atic review to identify re- 3 trials did
and meta- search priori- malaria pro-
analysis ties phylaxis
Fortification
Suchdev January 2 trials To assess the Clus- Pregnant Rural set- Interven- Hb concentration GRADE: maternal anaemia at
2015 2015 (1172 effects of pre- ter-RCTs women of ting in tion: MNP (g/L) at 32 weeks’ term or near term = very low,
pregnant natal home any gesta- Bangladesh for point- gestation other relevant outcomes = not
Multiple women) (point-of- tional age and Mexico of-use forti- assessed
micronu- use) fortifica- and parity fication of Any anaemia at
trient tion of foods Anaemia semi-solid 32 weeks’ gesta- Cochrane RoB 1. Both trials
powders with MNP and malaria foods con- tion were at unclear of bias for ran-
for home on maternal prevalence: taining at dom sequence generation. Al-
Maternal Hb (g/

(point-of- and newborn malaria not least 3 mi- location concealment was low
use) forti- endemic L) at term or near risk of bias. The risk of perfor-
health cronutri-
fication of term mance and detection bias was
ents, with
foods in 1 of them high in both trials.
Maternal
pregnant being iron, anaemia at term
women provided or near term (Hb
to women < 110 g/L at 34
during preg- weeks’ gestation
nancy or more)
Compari- Adjustments: not
son: no in- reported
89
(Review)
tervention
or place-
Library
Cochrane
bo, iron
and folic
acid supple-
ments, iron-
only sup-
plements,
folic acid-
Better health.
Informed decisions.
Trusted evidence.
only sup-
plements or
same MMNs
in supple-
ments
CHERG: Child Health Epidemiology Reference Group; FCM: ferric carboxymaltose; Hb: haemoglobin; HIV: Human Immunodeficiency Virus; ID: iron deficiency; IDA: iron deficiency
anaemia; IFA: iron folic acid; IPM: iron polymaltose; IS: iron sucrose; IV: intravenous; LNS: lipid-based nutrient supplements; MMNs: multiple micronutrients; MNP: micronutrient
powder; NAID: non-anaemic iron deficiency; RCTs: randomised controlled trials; RoBANS: Risk of Bias Assessment tool for Non-randomized Studies; UNIMMAP: United Nations
International Multiple Micronutrient Preparation.
Table 8. Characteristics of included systematic reviews: mixed populations

Review Date of Number Review ques- Trial de- Partici- Setting, Intervention and Relevant GRADE assessment of rele-
search of includ- tion/objec- signs in- pants anaemia and comparison outcomes vant outcomes
ed trials tive cluded malaria preva- (defini-
(number lence tion used Method used to assess risk
of partic- in the re- of bias and summary
ipants in- view, ad-
cluded) justed for
smoking
and alti-
tude)

Supplementation
Arabi 2020 January 14 trials To investi- RCTs Aged 17.5 USA (5 trials), Intervention: oral Haemo- GRADE: not assessed
2019 (10 to 276 gate the effect to 68 years Germany (3 tri- vitamin D sup- globin lev-
The effect partici- of vitamin D old (in- als), Poland (2 plements; such els, iron Cochrane RoB 1 tool used.
of vitamin pants) supplements cluding trials), Spain, as cholecalcifer- markers Low risk of bias in 9 trials,
D supple- on haemo- RCTs with India, Norway, ol, ergocalciferol (levels of moderate in 2 trials
mentation globin con- healthy Columbia and calcitriol ferritin,
on hemo- centration in adults, serum
globin con- participants anaemic Anaemia and Comparison: iron, and
centration: patients, malaria preva- placebo, For- transfer-
90
(Review)
Table 8. Characteristics of included systematic reviews: mixed populations (Continued)
a systematic aged 17.5 to chronic lence: not re- tified dry milk rin satura-
review and 68 years old kidney ported with 15 mg iron, tion)
Library
Cochrane
meta-analy- disease ampoules nor-
sis patients, mal saline + am-
heart fail- poules iron
ure pa-
tients, hy-
pertensive
patients,
Better health.
Informed decisions.
Trusted evidence.
critically
ill patients
and ath-
letes)
Basutkar January 4 trials To estimate RCTs Patients Norway, USA, Intervention: vi- Change in GRADE: haemoglobin =
2019 2018 (429 par- the efficacy with IDA India (2 trials), tamin D supple- serum fer- high, serum ferritin = high
ticipants) of vitamin D (20 to 45 community mentation ritin and
Vitamin D supplemen- years) centres and haemoglo- Cochrane RoB 1 tool
supplementation on pa- outpatient set- Comparison: bin levels
tation in tients with tings (3 trials); placebo
patients IDA (patients with
with iron IDA)
deficiency
anaemia: a
systematic
review and a
meta-analy-
sis
Casgrain February 41 trials To assess RCTs Healthy Switzerland, Intervention: iron Hb (g/dL) GRADE: not assessed
2012 2012 the effects of adult pop- Kuwait, USA supplement, for-
baseline iron ulation (15 trials), tified food, or rich Adjust- Scale designed by the EUR-
Effect of status, sex, (mean Spain, Mexico natural dietary ments: not RECA Network of Excellence
iron intake menopausal age ≥ 18 (2 trials), UK sources reported (on the basis of Cochrane

on iron sta- status, dura- years, with (5 trials), Thai- methods). Most trials were
tus: a sys- tion of inter- any base- land (2 trials), Comparison: rated at high risk of bias (24
tematic re- vention, iron line iron Brazil, Sri Lan- placebo or no di- trials) and the remainder at
view and form, and dai- status; ka, Sweden (2 etary interven- unclear risk of bias because
meta-analy- ly dose on the exclud- trials), Philip- tion of insufficient information
sis of ran- change in iron ing high- pines (2 trials), for an
domized status in re- ly trained Finland, New accurate assessment (17 tri-
controlled sponse to iron athletes, Zealand, Aus- als).
trials supplementa- regular tralia, China,
tion blood South Africa,
donors, Vietnam (2 tri-
and indi- als), Japan
91
(Review)
viduals Anaemia and
receiv- malaria preva-
Library
Cochrane
ing ery- lence: not re-
thropoi- ported
etin, with
chronic
disease, or
with GI in-
fections)
Better health.
Informed decisions.
Trusted evidence.
Gera 2007a February 55 trials To evaluate RCTs Children Asia (22 trials), Intervention: iron Hb (g/dL) GRADE: not assessed
or April (some tri- the effect of (aged from Africa (11 tri- supplementation
Effect of 2003 als con- iron supple- Clus- birth to 19 als), Europe (10 through the oral Adjust- Methodological quality as-
iron supple- tributed to mentation on ter-RCTs years, 31 trials), South or the parenter- ments: not sessment (A, B, C or D) us-
mentation > 1 analyt- Hb in children trials in in- America (8 al route or as for- reported ing the following domains:
on haemo- ic compo- through a sys- fants and trials), North mula, milk, or randomisations, allocation
globin re- nent) tematic re- preschool America (4 tri- cereals fortified concealment, follow-up and
sponse in view of trials children als) with iron blinding. Allocation con-
children: under cealment was adequate in
systemat- 6 years, Malaria: 11 an- Comparison: 12 analytic components
ic review of 25 trials alytic compo- placebo (trials in versus 73 others; attrition
randomised among nents in malar- which other mi- was < 10% in 57 versus >
controlled older chil- ia-endemic ar- cronutrients and 10% in 34; and 23 were dou-
trials dren) eas versus 80 drugs were simul- ble-blinded versus 25 others
not taneously admin-
None of istered were in-
the age Anaemia preva- cluded if the on-
groups lence: not re- ly difference be-
dominat- ported tween the exper-
ed (i.e. > imental and con-
60%) trol groups was
iron supplemen-
tation)

Gera 2009 January or 30 trials To study the RCTs Children Majority con- Intervention: iron Hb (g/dL) GRADE: not assessed
February (50 ana- effect of com- (aged from ducted in de- supplementation
Effect of 2006 lytic combining mul- birth to 18 veloping coun- in combination Adjust- Methodological quality as-
combining ponents tiple (2 or years) tries, with 2 or more ments: not sessment (A, B, C or D) us-
multiple mi- as some more) mi- other micronutri- reported ing the following domains:
cronutrients trials con- cronutrients None of Africa (14 trials), ents randomisations, allocation
with iron tributed to with Fe sup- the age Asia (11 trials), concealment, follow-up and
supplemen- > 1 com- plementa- groups South America Comparison: blinding. Allocation con-
tation on Hb parison) tion on Hb re- dominat- (4 trials), North placebo (trials cealment was adequate in
response sponse, when ed (i.e. > America (1 trial) in which other 12 analytic components ver-
in children: compared 60%) drugs were also sus 21 others; attrition was
systemat- with placebo simultaneous- < 10% in 18 versus > 10%
92
(Review)
ic review of and with Fe Malaria: 11 an- ly administered in 14; and 23 were double
randomized supplemen- alytic compo- were included if blinded versus 10 others
Library
Cochrane
controlled tation, in chil- nents in malar- the only differ-
trials dren ia-endemic ar- ence between the
eas versus 22 trial and the con-
not trol groups was
supplementation
Anaemia preva- with 2 or more
lence: not re- micronutrients,
Better health.
Informed decisions.
Trusted evidence.
ported for the second
objective, and Fe
plus 2 or more
micronutrients
for the first objec-
tive)
Silva Neto Not re- 12 trials (6 To compare RCTs Any (no re- Low and high- Intervention: for- Hb (g/L) GRADE: not assessed
2019 ported trials: 730 the effects of strictions income coun- tified foods or
children, a dietary in- based on tries: USA (3 tri- dietary plan; di- Final Cochrane RoB 1 tool. 7 of
Effects of 5 trials: tervention the par- als), Vietnam (2 etary interven- preva- the included trials were as-
iron supple- 164 ado- versus iron ticipants’ trials), Australia tion (i.e. an inter- lence of sessed as being at high risk
mentation lescents supplemen- sex, age or (1 trials), Chile vention that pro- anaemia of bias and only 5 at low risk
versus di- or adults, tation on Hb race) (1 trial), India vided a fortified of bias
etary iron Adjust-
1 trial: 85 and other (1 trial), Kenya food product or
on the nutri- ments: not
pregnant serum bio- (1 trial), Mexi- a dietary plan of-
tional iron reported
women) chemical pa- co (1 trial), New fering at least half
status: sys- rameters re- Zealand (1 tri- of the daily rec-
tematic related to the al), Sweden (1 ommended di-
view with iron nutrition- trial) etary allowances)
meta-analy- al status of
sis of ran- humans, in Anaemia and Comparison: iron
domized a standard malaria preva- supplementation
controlled treatment pe- lence: not re-
trials ported

riod (defined
as 12 weeks
or more fol-
low-up)
Smelt 2018 April 2016 7 trials To evaluate RCTs Communi- England (2 tri- Intervention: vit- Hb (g/dL) GRADE: not assessed
(from 32 the effect ty-dwelling als), Switzer- amin B12 or folic
The effect reports) of vitamin elderly land (1 trial), acid (all dosages Adjust- Cochrane RoB 1 tool. All tri-
of vitamin (1306 par- B12 and folic (aged 60 Denmark (1 tri- and all forms of ments: not als were rated at low risk of
B12 and folic ticipants) acid supple- + years); al), the Nether- administration) reported bias for random sequence
acid supplementation on specific lands (1 trial), generation, allocation con-
mentation haematolog- popula- Australia (1 tri- cealment and blinding of
participants and personnel.
93
(Review)
on routine ical parame- tions (e.g. al), Greece (1 Comparison:
haemato- ters in the trials in trial) placebo
Library
Cochrane
logical pa- elderly patients
rameters in with dia- Anaemia and
older peo- betes or malaria preva-
ple: an indi- with re- lence: not re-
vidual par- nal failure) ported
ticipant da- were ex-
ta meta- cluded
Better health.
Informed decisions.
Trusted evidence.
analysis
Tay 2015 January 3 trials To determine RCTs Anaemic Anaemia and Intervention: oral Hb (g/L) GRADE: not assessed
2014 (440 par- if oral iron elderly malaria preva- iron
Systemat- ticipants) therapy is ef- people lence: partici- Adverse Cochrane RoB 1 tool. Over-
ic review fective in el- aged 65 pants were el- Comparison: no effects all, risk of bias was rated as
and meta- derly people years and derly patients oral supplemen- high in 1 trial, moderate in 1
analysis: tation or placebo Adjust- trial and low in 1 trial.
with IDA over with anaemia
what is the ments: not
evidence reported
for oral iron
supplemen-
tation in
treating
anaemia in
elderly peo-
ple?
Tolkien 2015 March 43 trials To quantify RCTs Adults (in- No setting re- Intervention: sup- Hb GRADE: not assessed
2014 (6831 par- the odds of GI cluding ported plementation
Ferrous sul- ticipants) side effects in Cross-over pregnant with ferrous sul- GI side ef- Cochrane RoB 1 tool. Ran-
fate supple- adults relat- RCTs women in Anaemia and phate fects dom sequence generation
mentation ed to current 7 trials) malaria preva- was rated at low risk of bias
causes sig- lence: not re- Comparison: Individ- in 25 trials and high risk of
gold standard
nificant gas- ported, but 1 placebo or IV iron ual side ef- bias in 2. Allocation con-
oral iron ther-

trointestinal trial included fects cealment was rated at low
apy, namely
side-effects ferrous sul- anaemic partic- risk of bias in 19 trials and
Adjust-
in adults: a phate ipants high risk of bias in 2 trials.
ments: not
systematic Blinding was rated at low
reported
review and risk of bias in 17 trials and
meta-analy- high risk of bias in 24.
sis
Fortification
94
(Review)
Das 2019b August 43 stud- To assess the RCTs Men, Healthy people Intervention: Serum Hb GRADE: Hb = low, anaemia =
2018 ies (48 re- impact of women, in high-income MMN fortification level (g/ low, IDA = low, ID = low
Library
Cochrane
Food fortifi- ports) food fortifi- Clus- and chil- and low- and (3 or more mi- dL)
cation with (19,585 cation with ter-RCTs dren. Spe- middle-income cronutrients) by Cochrane RoB 1 tool for
multiple mi- partici- MMNs on cific pop- countries any food vehicle Anaemia RCTs
cronutri- Quasi-ran- (Hb < 11 g/ 5 trials: overall low risk of
pants, in- health out- ulations
ents: impact domised Anaemia and Comparison: a dL) bias, 34 trials: overall high
cluding comes in the such as
on health trials malaria preva- single micronutri- risk of bias.
17,878 general pop- older
outcomes lence: not re- ent or no fortifi- IDA (Hb Cochrane EPOC for non-
children) ulation, in- people,
Better health.
Informed decisions.
Trusted evidence.
CBA stud- < 11 g/
in general cluding men, pregnant ported cation RCTs and CBA studies, 4 tri-
ies dL with
population women and women, als: high risk
serum fer-
children ITS studies women
ritin < 15
of repro-
μg/L
ductive
age, and Potential
children adverse
at school outcomes
through
institu- Adjust-
tions were ments: not
includ- reported
ed. Crit-
ically-ill
people,
anaemic
people or
people di-
agnosed
with any
specific
diseases
were ex-
cluded.

Field 2020 Septem- 9 trials To determine RCTs General India (2 trials), Intervention and Hb con- GRADE: wheat flour forti-
ber 2019 (3166 par- the benefits popula- Brazil, Kuwait, comparison: centration fied with iron alone ver-
Wheat flour ticipants) and harms Clus- tion from Phillipines, Pak- (g/L) sus unfortified wheat flour:
fortification of wheat ter-RCTs any coun- istan, Sri Lan- • wheat flour Hb = very low, anaemia =
with iron flour fortifi- try aged ka, Bangladesh, fortified with Anaemia low, ID = moderate; wheat
for reduc- Qua- iron alone ver- (defined
cation with two years South Africa flour fortified with iron in
ing anaemia si-RCTs sus unfortified as haemo-
iron alone or and above combination with other
and improv- with other vi- Anaemia preva- wheat flour globin be- micronutrients versus un-
ing iron sta- tamins and lence: not re- (no micronu- low WHO fortified wheat flour: Hb
tus in popu- minerals on ported trients added) cut-off for = low, anaemia = low, ID =
lations anaemia, iron age moderate; wheat flour for-
95
(Review)
status and Malaria preva- • wheat flour and ad- tified with iron in combina-
health-relat- lence: 2 trials fortified with justed for tion with other micronutri-
Library
Cochrane
ed outcomes reported to iron in com- altitude as ents versus fortified wheat
in popula- be conducted bination with appropri- flour with same micronu-
tions over two in non-malar- other mi- ate) trients (but not iron): Hb =
years of age ia-endemic ar- cronutrients low, anaemia = very low, ID
eas; the remain- versus unfor- ID (as de- = very low
ing studies did tified wheat fined by
not report on flour (no mi- trialists, Cochrane RoB 1 tool for
Better health.
Informed decisions.
Trusted evidence.
malaria cronutrients based on a RCTs.
added) biomarker Most of the included trials
• wheat flour of were
fortified with iron sta- assessed as low or unclear
iron in com- tus) risk of bias for key elements
bination with of selection, performance or
Adverse reporting bias.
other mi- side ef-
cronutrients fects
versus fortified For chil-
wheat flour dren aged
with same mi- 2 to 11
cronutrients years old:
(but not iron) Diarrhoea
• wheat flour (3 liquid
fortified with stools in
iron alone ver- per day)
sus no inter-
vention; and Respira-
• wheat flour tory infec-
fortified with tions (as
iron in com- measured
bination with by trial-
other mi- ists)
cronutrients

versus no in-
tervention
Finkelstein August 3 tri- To inform RCTs Gener- Phillipines, In- Intervention: pro- Anaemia GRADE: not assessed
2019 2018 als (633 public health al pop- dia, Rwanda viding iron-bio- (Hb < 120
adoles- programmes ulation fortified staple g/L) Cochrane RoB 1 tool for
Iron biofor- cents and and to incor- (includ- Anaemia and crops that were RCTs. Most of the included
tification in- adults) porate biofor- ing preg- malaria preva- not genetically ID (serum trials were
terventions tification as nant or lence: not re- modified ferritin < assessed as low or unclear
to improve a strategy to lactating ported 15.0 μg/L) risk of bias for key elements
iron status target iron de- women) Comparison: con- of selection, performance or
and func- ficiency in at- ventional crops reporting bias.
96
(Review)
tional out- risk popula-
comes tions
Library
Cochrane
Garcia-Casal December 5 trials To assess the RCTs General Kenya, Mexico Intervention and Hb (g/L) GRADE: provision of maize
2018 2017 and (2610 par- effects of iron popula- (2 trials), Brazil, comparison: flour or maize flour prod-
January ticipants fortification Clus- tion old- Zambia Anaemia ucts fortified with iron plus
Fortification 2018 in RCTs, of maize flour, ter-RCTs er than 2 • maize flour (defined other vitamins and min-
of maize 849 in un- corn meal years of Anaemia preva- or maize flour as Hb be- erals versus unfortified
flour with Uncon- lence: < 20% in products forti- low WHO
controlled and fortified age (in- maize flours or maize flour
Better health.
Informed decisions.
Trusted evidence.
iron for trolled be- 3 trials, > 40% fied with iron cut-off, ad-
before-af- maize flour cluding products: Hb = very low,
controlling fore-after in 1 trial and alone versus justed for
ter trials) products on pregnant anaemia = very low, ID =
anaemia trials not reported in no interven- altitude
anaemia and women), very low
and iron de- iron status in from any 1 trial tion and
(data only
ficiency in the general country • maize flour smoking, Cochrane EPOC risk
extracted Malaria preva-
populations population or maize flour as appro- of bias tool.
for RCTs) lence: 2 trials products forti- priate)
in malaria set- fied with iron Overall risk of bias was low
tings, 3 trials plus other vita- IDA (as de- in 1 trial, and high in the re-
did not report mins and min- fined by maining trials due to high
on malaria en- erals versus no trialists) risk or unclear risk of bias
demicity intervention for random sequence gen-
ID (as de- eration, allocation conceal-
• maize flour fined by ment and blinding.
or maize flour trialists,
products for- based
tified with on a bio-
iron alone ver- marker of
sus unforti- iron sta-
fied maize tus)
flours or maize
flour products Any ad-
(not contain- verse ef-
ing iron or any fects (in-
other vitamin cluding

and minerals) constipa-
• maize flour tion, nau-
or maize flour sea, vom-
products forti- iting,
fied with iron heartburn
plus other vi- or diar-
tamins and rhoea, as
minerals ver- measured
sus unforti- by trial-
fied maize ists)
flours or maize
flour products Adjust-
ments: ad-
97
(Review)
(not contain- justed for
ing iron nor altitude as
Library
Cochrane
any other vita- appropri-
min and min- ate
erals)
Gera 2012 March 60 trials The objec- RCTs Apparent- Most of the tri- Intervention: ad- Hb (g/dL) GRADE: not assessed
2012 (11,750 tives were to ly healthy als were from ditional dietary
Effect of iron-forti- evaluate: i) Qua- (non-dis- low- and mid- iron through the Anemia Cochrane RoB 1 tool. Allo-
Better health.
Informed decisions.
Trusted evidence.
iron-fortified partic- the effect of si-RCTs eased) in- dle-income route of food for- (%, as de- cation concealment was ad-
fied foods ipants and iron fortifi- dividuals, countries: tification or bifor- fined in equate in 25 analytic com-
on hema- Clus- individ- ponents versus 52 others;
9077 con- cation on Hb families, Asia (41 trials), tification
tologic and ter-RCTs ual trials, sequence generation was
trol partic- and serum or com- Africa (13 trials),
biological ipants) ferritin and munities South America Comparison: sim- account- adequate in 14 versus 63
outcomes: the preva- irrespec- (14 trials), Eu- ilar food without ed for age others; blinding was ade-
systemat- (85 ana- lence of ID tive of age rope (9 trials), iron fortification and sex quate in 52 versus 25 oth-
ic review of lytic com- and anaemia; and sex Australia (1 tri- differ- ers; selective outcomes was
randomized ponents ii) the possi- considera- al), North Amer- ences for judged yes in 62 versus 15
controlled as some ble predictors tions ica (7 trials) defining others
trials trials con- of a positive Hb cut-off
tributed to Hb response; Malaria: 6 an- concentra-
> 1 com- iii) the effect alytic compo- tions)
parison) of iron fortifi- nents in malar-
ia-endemic ar- ID (%, as
cation on zinc
eas versus 71 defined in
and iron sta-
not individual
tus; and iv)
trials)
the effect of
Anaemia preva-
iron-fortified Adverse
lence: not re-
foods on men- effects
ported
tal and motor (any, as
development, defined in
anthropo- individual
metric mea- trials)

sures, and in-
fections. Adjust-
ments: not
reported
Hess 2016 December 14 trials To investi- RCTs Children 11 trials in Asia: Intervention: mi- Hb (g/dL) GRADE: not assessed
2013 (8674 par- gate existing and adults India (4 trials), cronutrient-forti-
Micronutri- ticipants) evidence on Clus- from 5 to Vietnam (3 tri- fied condiments Anaemia Risk of bias assessment con-
ent fortified the impact of ter-RCTs 50 years als), China (2 or noodles prod- rate (be- ducted according to 'CRD’s
condiments micronutri- trials), Cam- uct. Fortified tween 11 Guidance for Undertaking
and noodles ent-fortified bodia (1 trial), condiments in- g/dL and Reviews in Health Care': ad-
to reduce condiments cluded: condi- 13 g/dL, equate sequence genera-
98
(Review)
anemia in and noodles Thailand (1 tri- ments, salt, sea- depending tion, allocation conceal-
children and on haemoglo- al) sonings, soy on age) ment and blinding; incom-
Library
Cochrane
adults—a bin, anaemia, sauce, fish sauce, plete outcome data ad-
literature and function- 3 trials in Africa bouillon, sprin- Adjust- dressed; no selective report-
review and al outcomes (Morocco, kles and powder. ments: not ing. The risk of bias for the
meta-analy- in children Ghana, South Micronutrients reported investigated outcomes of
sis and adults Africa) for fortification “haemoglobin change” and
(aged 5 to 50 included: iron, vi- “anaemia rates” was un-
Malaria preva-
years) tamins, zinc, io- clear in most of the trials.
Better health.
Informed decisions.
Trusted evidence.
lence: not re-
dine, folate, calci-
ported
um, phosphorus,
Anaemia preva- magnesium and
lence: median selenium.
of 46% at base-
Comparison:
line
non-fortified
condiments and
noodles
Huo 2015 June 2014 16 trials To assess RCTs Any Chi- Chinese popu- Intervention: Anemia GRADE: not assessed
(16,819 the effect nese pop- lation: 5 trials NaFeEDTA-forti- rate and
Effect of partici- of NaFeED- Clus- ulation in poor rural vil- fied soy sauce Hb con- Cochrane RoB 1 tool. Ran-
NaFeED- pants) TA-fortified ter-RCTs in which lages, 8 trials in centra- dom sequence generation
TA-fortified soy sauce anaemia schools, and 3 Comparison: tions (ac- was adequate in 10 trials
soy sauce on anaemia is a pub- trials in hospi- non-fortified soy cording to and allocation concealment
on anemia prevalence in lic health tals sauce groups WHO-de- in 13 trials. Performance
prevalence the Chinese problem fined cut- bias was low in 12 trials,
in China: a population Anaemia: all off values and detection and reporting
systemat- trials included for differ- bias were low in all trials.
ic review anaemia-risk ent popu-
and meta- populations lations)
analysis of
randomized Malaria preva- Adjust-
controlled lence: not re- ments: not

trials ported reported
Peña-Rosas December 17 stud- To determine RCTs General Any countries; Intervention: Hb (g/L), GRADE: Hb = low, anaemia
2019 2018 ies (10,483 the benefits popula- anaemia preva- rice fortified with anaemia = low, ID = low, diarrhoea
partici- and harms of Clus- tion old- lence: 5% to at least one mi- (WHO cut- = very low, any adverse ef-
Fortification pants) rice fortifica- ter-RCTs er than 62% in children, cronutrient or a off or as fects (hookworm infection
of rice with tion with vita- two years 21% in women, combination of defined by risk) = low
vitamins Qua-
mins and min- of age (in- and 34% in several micronu- authors),
and miner- si-RCTs The EPOC risk of bias tool
erals (iron, vi- cluding teenagers; trients (iron, folic ID, diar-
als for ad- tamin A, zinc pregnant malaria preva- acid, zinc, vita- rhoea, and used for risk of bias assess-
Non-ran-
dressing mi- or folic acid) women) lence: not re- min A or other vi- any ad- ment. Funnel plots used to
domised
on micronu- ported but one verse ef- assess the reporting bias.
99
(Review)
cronutrient trient status controlled study conduct- tamins and min- fects; ad- All CBA studies had a high
malnutrition and health- trials, ob- ed in a malar- erals) justment: risk or unclear risk of bias in
Library
Cochrane
related out- servation- ia-endemic area yes most domains.
comes in the al studies Comparison: un-
general popu- (cohort fortified rice or no
lation studies, intervention
CBA stud-
ies, ITS
studies)
Better health.
Informed decisions.
Trusted evidence.
Ramírez- Not re- 14 trials To assess the RCTs Any partic- Low- and mid- Intervention: DFS Hb (g/L) GRADE: not assessed
Luzuriaga ported (45,995 impact of DFS ipants dle-income
2018 partici- on biomark- Qua- countries: India Comparison: con- Anaemia EPHPP quality assessment
pants) ers of iron si-RCTs (10 trials), Mo- trol salt (iodised tool; 3 trials were rated
Impact of salt) IDA at overall strong quality
status, and rocco (2 trials),
double-for- Clus- (strong for selection bias,
the risk of Côte D’Ivoire (1 Adjust-
tified salt ter-RCTs trial design, confounders,
anaemia and trial), Ghana (1 ments: not
with iron IDA trial) blinding, data collection
reported
and iodine methods, withdrawals and
on hemo- Anaemia and dropouts, intervention in-
globin, ane- malaria preva- tegrity and robustness of
mia, and lence: not re- the analysis), 3 moderate
iron defi- ported and 8 weak
ciency ane-
mia: a sys-
tematic re-
view and
meta-analy-
sis
Sadighi Febru- 101 stud- To assess the Controlled Males or Cameroon, Intervention: di- Hb level GRADE: not assessed
2019 ary/ March ies (52 effectiveness trials and females of Chile, China, etary fortifica- (g/L)
2019 controlled of iron-forti- before–af- all ages Costa Rica, Côte tion of flour (e.g. Cochrane EPOC statement.
Systemat- trials, 49 fied flour on ter studies d’Ivoire, Den- wheat, maize, or Anaemia Of the 52 trials included in

ic review before-af- iron status mark, India, rice), either in a the meta-analysis, 37 were
and meta- (data only IDA of overall low risk of bias
ter design) Iran, Jordan, raw form or in a
analysis of extracted Kazakhstan, cooking process, and the remaining 15 of
ID
the effect for RCTs) Kenya, Kuwait, with iron or with high risk.
of iron-forti- Mongolia, Mo- iron and other Adjust-
fied flour on rocco, Norway, micronutrients ments: no
iron status South Africa, reported
of popula- Sri Lanka, Tajik- Comparison: any
tions world- istan, Thai-
wide land, UK, USA,
Uzbekistan,
100
Venezuela, Viet-
(Review)
nam, and Zam-
bia
Library
Cochrane
Tablante June 2018 5 trials To evaluate RCTs Partic- General popula- Intervention: Hb level GRADE: Hb = low, anaemia =
2019 (1182 par- the health ipants tion; wheat flour or (g/L) low
ticipants) benefits and Non-RCTs from the wheat flour prod-
Fortification (3 non- safety of folic general Anaemia and ucts fortified with Anaemia Cochrane RoB 1 tool
of wheat ITS malaria preva-
RCTs, 2 acid forti- popula- folic acid (plus
and maize ITS) fication of tion, who lence: not re- other vitamins
Better health.
Informed decisions.
Trusted evidence.
flour with wheat and were two ported and minerals)
folic acid for maize flour years of
population (i.e. alone or age and Comparison: un-
health out- in combina- older (in- fortified wheat
comes tion with oth- cluding flours or wheat
er micronu- pregnant flour products
trients) on fo- and lac- (not containing
late status tating folic acid nor any
and health women), other vitamins
outcomes in and from and minerals)
the overall any coun-
population, try
compared
to wheat or
maize flour
without folic
acid (or no in-
tervention).
Yadav 2019 August 10 studies To study the RCTs Partici- India (5 tri- Intervention: DFS Hb GRADE: not assessed
2016 (3219 par- efficacy of pants of als), Maroc- (iron and iodine)
Meta-analy- ticipants) DFS as com- all age and co (2 trials), Preva- Cochrane RoB 1 tool. Allo-
sis of effi- pared to IS gender Ghana (2 trials), Comparison: IS lence of cation concealment was ad-
cacy of iron in improving Cote d’Ivoire anaemia equate in 5 trials, blinding
and iodine of participants and study

iron nutrition (anaemia and
fortified salt Preva- personnel in 8 trials, and
status malaria preva-
in improving lence of 7 trials addressed incom-
lence: not re-
iron nutri- IDA plete outcome data. Ran-
ported)
tion status dom sequence generation
Preva-
was mentioned in only 1 tri-
lence of ID
al. Details about blinding of
Adjust- outcome assessment were
ments: not not provided in any of the
reported trials.

101
(Review)
Geerligs May 2002 3 trials To complete RCTs People Low-income Intervention: Change in GRADE: not assessed
2003 (784 par- a systemat- in low- countries: food prepared in Hb con-
Library
Cochrane
ticipants) ic review of income Ethiopia, Brazil, cast iron pots centration Delphi list used as a means
Food pre- the effect of countries Malawi for quality assessment. Ran-
pared in preparing (minimum Comparison: Adjust- dom sequence generation
iron cook- food cooked age was Malaria: 1 trial food prepared ments: not was adequate in all trials,
ing pots as in iron pots on set at 4 conducted in in non-cast iron reported allocation concealment on-
an interven- haemoglobin months) malaria-endem- pots ly described in 1 trial. 2 tri-
tion for re- concentra- ic area als reported blinding of as-
Better health.
Informed decisions.
Trusted evidence.
ducing iron tions and to sessors, but none of the tri-
deficiency Anaemia preva- als blinded care provider or
assess com-
anaemia in lence: not re- participants.
pliance with
developing ported
pot use
countries: a
systematic
review
CBA: Controlled before-after; CRD: Centre for Reviews and Dissemination; DFS: double-fortified salt; EPOC: Effective Practice and Organisation of Care; EPHPP: Effective Public
Health Practice Project; EURRECA: EURopean micronutrient RECommendations Aligned; Fe: ferrum (iron); GI: gastrointestinal; Hb: haemoglobin; ID: iron deficiency; IDA: iron
deficiency anaemia; IDNA: iron-deficient non-anaemic; IS: iodine fortified salt; ITS: interrupted time series; IV: intravenous; MMN: multiple micronutrients; NaFeEDTA: sodium iron
ethylenediaminetetraacetate; RCTs: randomised controlled trials; WHO: World Health Organization.
Table 9. Characteristics of interventions: infants (aged 6 to 23 months)

Review Intervention Prevention Population (mean age, base- Dose (mean range) or Frequency Start of in- Adherence to
or treatment line anaemia status/preva- composition or form tervention or intervention
lence, known micronutrient de- of application (includ- duration (or
ficiencies) ing compound, formu- both)
lation)
Supplementation

Abdullah 2013 Oral iron Treatment Non-anaemic iron-deficient Oral ferrous sulphate (3 Once or twice Duration: 3 to Reported in 1
children aged 1 to 5 years mg/kg per day) daily 4 months trial
Efficacy of oral iron (mean age = 6 months to 30
therapy in improv- months)
ing the developmen-
tal outcome of pre-
school children with
non-anaemic iron
deficiency: a system-
atic review
102
(Review)
Table 9. Characteristics of interventions: infants (aged 6 to 23 months) (Continued)
Das 2019a LNS with Prevention 12 trials: children aged 6 10 trials: SQ LNS, 110 to Daily Start of inter- Not reported
complemen- months to 18 months (mean 120 kcal/day (20 g dose); vention: 5.5
Library
Cochrane
Preventive lipid- tary food at age: 5.9 months to 9.9 months); 4 trials: MQ LNS, 250 to months to 6
based nutrient sup- point-of-use 4 trials: children aged 6 months 500 kcal/day (45 g to months. How-
plements given with to 24 months (mean age: not 90 g dose); 2 trials, SQ ever most
complementary specified); 1 trial: children aged and MQ LNS; 1 trial: SQ studies were
foods to infants and 6 months to 36 months (mean for children aged 6 to not described.
young children 6 to age: 24 months) 12 months and MQ for Duration: 7
23 months of age for children aged 12 to 18 months to 18
Better health.
Informed decisions.
Trusted evidence.
health, nutrition, and Baseline anaemia status: not months months
developmental out- reported
comes
Known MN deficiencies: not re-
ported
Dekker 2010 Zinc Treatment Children 0 to 15 years (mean Typically 10 mg or 20 mg Daily Duration: 4 Not reported
age at baseline = 32 months, zinc per day months to 15
Zinc supplementa- the majority of the trials com- months
tion in children is not menced between 6 and 23
associated with de- months; 3 trials conducted
creases in hemoglo- among anaemic children, 3 tri-
bin concentrations als among children with malar-
ia, 1 among HIV-1–infected chil-
dren, 1 among children suffer-
ing from diarrhoea, 1 among
children with protein-energy
malnutrition, and 1 trial among
children who were
zinc deficient)
Pasricha 2013 Oral iron Prevention Children aged 4 to 23 months Typically provided as Daily Duration: Adherence
(8 trials included children with ferrous salts (ferrous sul- 1 week to not reported
Effect of daily iron anaemia, ID or IDA, most trials phate in 22 trials) 14 months in 11 trials. In

supplementation on unknown) (majority be- another 11 tri-
health in children Dose: 12.5 mg or less, tween 3 and 6 als, there was
aged 4-23 months: 12.6 mg to 30 mg, 31 mg months) no difference
a systematic review to 59 mg, > 60 mg per in adherence
and meta-analysis day between iron
of randomised con- and control
trolled trials group.
Petry 2016b Iron supple- Prevention Children were 6– to 23 months Iron dose: ≤ 15 mg/day Daily or 3 or Not reported Not reported
mentation, old (74 trials, apparently more times
The effect of low fortification healthy) Supplements defined as per week
dose iron and zinc compounds, which are
103
(Review)
intake on child mi- or biofortifica- Baseline anaemia status/preva- routinely consumed sep-
cronutrient status tion lence: apparently health, but arately from a normal
Library
Cochrane
and development may suffer from anaemia meal, including tablets,
during the first 1000 pills, drops, capsules,
days of life: a sys- Known MN deficiencies: appar- syrups, drinks, biscuits,
tematic review and ently healthy, but may suffer and LNS
meta-analysis from ID or zinc deficiency
Better health.
Informed decisions.
Trusted evidence.
Pratt 2015 MN sprinkles, Prevention Infants aged 3 to 36 months MN sprinkles: iron dose Fortification: Duration: Not reported
iron-fortified of 12.5 mg (2 trials) daily average 6
A review of the milk, iron sup- Baseline anaemia status/preva- Iron-fortified milk: fer- months
strategies used to re- plementa- lence: not reported rous gluconate 5.28 mg Supplementa-
duce the prevalence tion and food- to 5.8 mg (2 trials) tion: daily or
of iron deficiency Known MN deficiencies: not re- weekly
based strate- Iron supplementation:
and iron deficiency ported
gies 10 mg to 12.5mg (2 tri-
anaemia in infants als)
aged 6-36 months
Fortification
Dewey 2009 Home fortifi- Prevention Infant and young children aged Sprinkles: 12.5 mg/ Daily or sev- Duration: 6 Only few trials
cation of com- and treat- 4 to 36 months (anaemic at day to 80 mg/day; Iron eral times per weeks to 20 reported. Ad-
Systematic review plementary ment baseline in 5 treatment trials drops: 12.5 mg/day to 40 week months herence was
and meta-analysis foods with and non-anaemic in 11 preven- mg/day high when re-
of home fortification MNP (sprin- tion trials) ported
of complementary kles), crush- Sprinkles + folic acids +
foods able tablets Baseline anaemia status/preva- MMN + fortified supple-
and lipid- lence: reported, Known MN de- ment: 12.5 mg/day to 30
based or soy- ficiencies: not reported mg/day
based prod-
ucts
Eichler 2012 MN fortified Prevention Infants and children from 6 MN food with 1.8 mg/ Daily Mean fol- Not reported

milk or cereal months to 5 years of age (mean day to 27.5 mg/day iron low-up pe-
Effects of micronu- food age ranged from 6 months to 23 riod: 8.25
trient fortified milk months at inclusion, upper age months (2.2
and cereal food for limit was 3 years in 1 trial, me- to 12 months)
infants and children: dian of anaemia rates at base-
a systematic review line was 36% from 9 trials)
Matsuyama 2017 Fortified milk Prevention Children (mean age at baseline Dose: not reported Not specified Duration: 4 to Adherance
(most com- = 6 months to 22.4 months, 1 12 months checked in
Effect of fortified mon with trial = 29 months to 31 months Type of iron used: fer- most included
milk on growth and iron, vitamin at baseline, some trials includ- rous sulphate (3 trials), trials
nutritional status ferrous gluconate (2),
104
C, zinc, fatty
(Review)
in young children: acids, vitamin ed anaemic children at base- ferrous lactate (1), un-
a systematic review D, probiotics line) clear in remaining trials
Library
Cochrane
and meta-analysis or synbiotics)
Salam 2013 MNP Prevention Children aged 6 months to 11 MNP: vitamins and min- Daily Duration: 2 to Not reported
years (most trials children aged erals, most trials used 24 months
Effectiveness of mi- 6 months to 6 years, 2 trials up 12.5 mg iron (range = 2.5
cronutrient powders to 11 years) mg to 30 mg) as ferrous
(MNP) in women and fumarate
Better health.
Informed decisions.
Trusted evidence.
children Baseline anaemia status/preva-
lence: not reported

ported
Suchdev 2020 MNPs, includ- Prevention Apparently healthy infants and MNP with 12.5 mg ele- Daily Duration: 2 No studies re-
ing at least young children aged 6 months mental iron in 14 trials, months to 44 ported data
Point-of-use fortifica- iron, zinc and to 23 months 10 mg in 8 trials, 6 mg months on outcome
tion of foods with mi- vitamin A in 1 trial, 30 mg in 1 tri- adherence
cronutrient powders Baseline anaemia status/preva- al. MNP with 9 mg of fer-
containing iron in lence: mixed status rous orthophosphate,
children of preschool 6 mg of ferrous lactate
and school age Known MN deficiencies: not re-
and 2.5 mg of NaFeEDTA
ported
in 1 trial each
Kristjansson 2015 Supplemen- Prevention Children aged 3 months to 5 Variet of food was pro- Daily Duration: 3 Method of
tary feeding years (> 60% of children were vided (milk, bread, fruit, months to 32 adherence
Food supplementa- (provision of under 2 years, high proportion vegetables, rice and months reported in
tion for improving energy and of children had low weight-for- lentils, or provided a for- most trials
the physical and psy- macronutri- age z-scores or height-for-age z- tified cookie, etc.)
chosocial health of ents) with scores)
socio-economical- or without 11 trials: ready-to-use

ly disadvantaged added mi- therapeutic feeding acid
children aged three cronutrients with or without other
months to five years foods
1 trial: bread with milk
4 trials: cereal, flours or

vegetable mixture, usu-
ally with milk
7 trials: locally available

foods such as fruit, veg-
105
(Review)
etables, rice and lentils,
or provided a fortified
Library
Cochrane
cookie
2 trials: iron-fortified
cereal
1 trial: meat
1 trial: hot lunches, nu-
Better health.
Informed decisions.
Trusted evidence.
tritious snacks, and vita-
min
supplementation
16 trials: fortified foods
Shapiro 2019 Animal-source Prevention Children aged 6-9 months Animal-source food Not specified 5 months to Not reported
food con- (beef, fish, fish powder, 12 months
A systematic review sumption ver- Baseline anaemia status: not pork, egg, caterpillar ce-
investigating the re- sus control reported real)
lation between ani- (e.g. non-ASF
mal-source food con- Know micronutrient deficien-
or no inter-
sumption and stunt- cies: not reported
vention)
ing in children aged
6-60 months in low
and middle-income
countries
ID: iron deficiency; IDA: iron deficiency anaemia; LNS: lipid-based nutrient supplements; MN: micronutrient; MMN: multiple micronutrient; MNP: micronutrient powders; MQ:
medium quantity; NaFeEDTA: sodium iron ethylenediaminetetraacetic acid; SQ: small quantity.
Table 10. Characteristics of interventions: preschool and school-aged children (aged 2 to 10 years)

Review Intervention Prevention Population (mean age, base- Dose (mean range) or com- Frequency Start of in- Adherence to
or treatment line anaemia status/preva- position or form of appli- tervention or intervention
lence, known micronutrient de- cation (including com- duration (or
ficiencies) pound, formulation) both)
Supplementation
Low 2013 Oral iron Prevention or Children 5 years to 12 years Oral iron supplementation: Daily Duration: 1 Reported
treatment 5 mg/day to 400 mg/day or month to 12 in 21 trials,
Effects of daily Baseline anaemia status/preva- 3 mg/kg/day to 10 mg/kg/ months adherence
iron supplemen- lence: some trials included day (most trials ferrous sul- ranged from
tation in prima- anaemic children
106
fate, but also iron citrate,

(Review)
Table 10. Characteristics of interventions: preschool and school-aged children (aged 2 to 10 years) (Continued)
ry-school-aged Known MN deficiencies: some ferrous fumarate, iron poly- 80% to 90% in
children: system- trials included ID or IDA chil- maltose, ferrous gluconate, most trials
Library
Cochrane
atic review and dren ferrous dextran)
meta-analysis of
randomized con-
trolled trials
De-Regil 2011 Intermittent Prevention or Children under 12 years of age Total elemental iron per Twice/week Duration: 6 Adherence
supplementa- treatment week: 7.5 mg to 200 mg (fer- (9 trials), 3 weeks to 3 tends to be
Better health.
Informed decisions.
Trusted evidence.
Intermittent iron tion with iron Baseline anaemia status/preva- rous sulphate in almost all times/week (2 months (15 higher in chil-
supplementation alone or with lence: 7 trials included only trials, most trials supple- trials), once/ trials), > 3 dren receiv-
for improving nu- other nutri- anaemic children, 3 trials only mented only with iron, 1 week (remain- months to 1 ing intermit-
trition and devel- ents non-anaemic children, in the trial in combination with ing trials) year (18 trials) tent iron sup-
opment in chil- remaining trials, the baseline 30 mg vitamin C, 5 trials in plementation
dren under 12 prevalence of anaemia ranged combination with folic acid, compared
years of age between 15% and 90% 4 trials with MMNs) with those re-
ceiving daily
Known MN deficiencies: some
iron supple-
trials included children with ID
ments (not
statistically
significant)
Mayo-Wilson Orally admin- Prevention Children of 6 months to 12 Zinc supplements provided Ranging from Trials provid- Poor or non-
2014a istered zinc years of age (mean age = 28 zinc as a solution or syrup daily to week- ed zinc for < 2 compliance
given as a months) (46 trials), pill or tablet (17 ly months (8 tri- for some par-
Zinc supplemen- supplement trials), capsule (6 trials), or als), 2 months ticipants re-
tation for pre- Baseline anaemia status/preva- powder (2 trials) to < 6 months ported in 4 tri-
venting mortali- lence: 1 trial included anaemic Zinc dose administered dai- (22 trials), 6 als
ty, morbidity, and children ly dose equivalents of < 5 months to <
growth failure mg (5 trials), 5 mg to < 10 12 months (33
in children aged Known MN deficiencies: median
mg (19 trials), 10 mg to < 15 trials), and
6 months to 12 of mean baseline zinc concen-
mg (30 trials), 15 mg to < 20 11 months or
years of age tration was 72.5 μg/dL
mg (8 trials), and 20 mg or more (16 tri-

more (12 trials) als)
Thompson 2013 Oral iron Prevention or Children 2 years to 5 years Iron: 5 mg/day to 50 mg/day At least 5 days Duration: 28 Adherence re-
treatment (most trials used ferrous per week days to 15 ported in 2 tri-
Effects of daily Baseline anaemia status/preva- sulphate, some used sodi- months als: consump-
iron supplemen- lence: 6 trials included anaemic um iron edetate, ferric am- tion ranged
tation in 2- to 5- children, 7 trials mixed or un- monium citrate, ferrous glu- from 80% to
year-old children: known conate) 97%
systematic re-
view and meta- Known MN deficiencies: chil-
analysis dren with ID in 4 trials
107
(Review)
Fortification
Library
Cochrane
Aaron 2015 Non-dairy Prevention 9 trials: school-aged children MMN contained vitamin Daily Duration: 8 Reported in 4
MMN-fortified (mean age = 5 years to 18 A, vitamin C, iron and zinc weeks to 8.5 trials, but not
Multiple-mi- beverages years); 1 trial: pregnant women in all trials and also vita- months further speci-
cronutrient for- (mean age = 25 years) min B12, vitamin E, folate, fied
tified non-dairy niacin, vitamin B6 and B2 Start of in-
beverage inter- Baseline anaemia status/preva- and iodine in most trials (intervention
ventions reduce lence: not reported, most stud- for pregnant
Better health.
Informed decisions.
Trusted evidence.
complete information on
the risk of anemia ies excluded children with low quantities and chemical women: 12
and iron deficien- Hb level (60 g/L to 80 g/L) forms of micronutrients) weeks to 34
cy in school-aged weeks' gesta-
children in low- Known MN deficiencies: not re- tion and dura-
middle income ported tion 8 weeks
countries: a sys-
tematic review
and meta-analy-
sis
Das 2013a Food fortifi- Prevention 3 trials: school children (2 years Zinc oxide in cereals (3.75 Not reported Duration: 3 Not reported
cation (bread, to 11 years) mg/oz) and zinc acetate in months to 9
Systematic re- porridge, ce- bread (400 mg/loaf) or por- months
view of zinc forti- real) with zinc Baseline anaemia status/preva- ridge (5 mg/100 g)
fication studies lence: healthy or unknown
Known MN deficiencies: healthy

or with asymptomatic zinc defi-
ciency
De-Regil 2017 MNP for Prevention Preschool and school-aged chil- 3 trials: formulation of 14 vi- Daily Duration: 8 Reported in
point-of-use dren (6 trials: only children up tamins and minerals weeks to 12 1 trial (no dif-
Point-of-use forti- fortification to 59 months of age, 4 trials: weeks ference be-
fication of foods age 5 years and older, 3 trials: 2 trials: formulation with 6 tween inter-
with micronu- vitamins and minerals

both younger and older than 59 vention and
trient powders months of age) control group)
containing iron Remaining trials: different
in children of Baseline anaemia status/preva- formulations (range = 2 to
preschool and lence: 7 trials excluded children 18 vitamin and minerals)
school age with low Hb values

ported
Eichler 2019 Central- Prevention 24 trials: children (aged 5 years Centrally-processed forti- Not reported Not reported Not reported
ly-processed to 12 years) and adolescents fied dairy products and for-
108
fortified dairy (aged 12 to 15 years) (mean tified cereals, using any for-
(Review)
Health effects of products and age: 6 years to 13.3 years, more tification strategy. Dairy
micronutrient fortified cere- than 60% fell within the age products included forti-
Library
Cochrane
fortified dairy als, using any group of 2 years to 10 years) fied fresh milk; centrally
products and ce- fortification processed milk or other
real food for chil- strategy Baseline anaemia status: not dairy products (such as yo-
dren and adoles- reported ghourt, milk powder and
cents: a system- cheese). Cereals included,
atic review for example, fortified wheat
ported
flour or maize (corn)
Better health.
Informed decisions.
Trusted evidence.
Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; MN: micronutrient; MMNs: multiple micronutrients, MNP: micronutrient powder.
Table 11. Characteristics of interventions: adolescent children (aged 11 to 18 years)

or treatment line anaemia status/prevalence, composition or form tervention or intervention
known micronutrient deficien- of application (includ- duration (or
cies) ing compound, formu- both)
lation)
Supplementation
Fernández-Gaxio- Oral iron Prevention or Menstruating women (range 6 60 mg iron (10 mg to Once a week Duration: 3 Reported in 6
la 2019 alone or with treatment years to 49 years, but > 60% of maximum 120 mg), fer- (5 trials twice months or less trials, no evi-
other vita- the trials included women under rous sulphate (in most a week) (13 trials), 3.5 dence of a dif-
Intermittent iron mins and min- 18 years, most trials involved a trials) months (3 tri- ference be-
supplementa- erals mix of anaemic and non-anaemic als), 4 months tween groups
tion for reducing women) (6 trials), 5
anaemia and its months (1 trial),
associated im- 6 months (1 tri-
pairments in ado- al), 12 months
lescent and adult (1 trial)

menstruating
women
Neuberger 2016 Oral iron Treatment or Children less than 18 years of age Mean iron supplementa- Daily Mean duration Adherence
Oral iron with prevention tion dose: 2 mg/kg/day of treatment: reported in
Oral iron supple- or without Baseline anaemia status: not re- 4.5 months (1 to 20 trials and
ments for chil- folic acid ported. Known MN deficiencies: 12 months) the average
dren in malar- Oral iron with not reported overall adher-
ia-endemic areas antimalarial ence to all tri-
prophylaxis al drugs was
good (89%)
109
(Review)
Table 11. Characteristics of interventions: adolescent children (aged 11 to 18 years) (Continued)
Salam 2016 MN supple- Prevention or Adolecent population (11 years MN supplementation: MN supple- MN supplemen- Not reported
mentation treatment to 19 years old, most trials in- mentation: tation
Library
Cochrane
Interventions to and nutrition cluded girls, 9 included boys and 13 trials = iron/iron folic
improve adoles- in pregnancy girls) acid supplementation daily or week- duration: not
cent nutrition: alone ly reported
a systematic re- Baseline anaemia status/preva-
view and meta- lence: 2 trials included anaemic 9 trials = iron/iron folic Nutrition in Nutrition in
analysis girls, 29 not reported acid in combination with pregnancy: pregnancy
other MNs
Better health.
Informed decisions.
Trusted evidence.
Known MN deficiencies: un- not reported start: between
known 2 trials = multiple MNs 20 weeks to 27
alone weeks' gesta-
tion
2 trials = zinc supple-
mentation 5 trials: sup- Duration: until
plemented with calcium delivery
and vitamin D
Nutrition in pregnancy:
mainly provision of MN
supplementation such
as calcium and zinc, in
addition to the routine
iron folic acid supple-
mentation or nutritional
education sessions
Salam 2020 MN sup- Prevention 10 studies: 10,802 adolescents Supplementaion of iron, Daily 10 weeks to 2 Not reported
plementa- aged 10 years to 19 years calcium, folic acid, zinc, years
Effects of pre- tion/fortifica- vitamin A, vitamin D Weekly
ventive nutrition tion (any MN Baseline anaemia status; not re-
interventions alone or in ported
among adoles- combination)
cents on health This review excluded hospi-

and nutritional talised adolescents and ado-
status in low- and lescents with any pre-existing
middle-income health condition
countries
MN: micronutrient
110
(Review)
Table 12. Characteristics of interventions: non-pregnant women of reproductive age (aged 19 to 49 years)
Review Intervention Prevention Population (mean Dose (mean range) or composition Frequency Start of in- Adherence to
or treatment age, baseline anaemia or form of application (including tervention or intervention
Library
Cochrane
status/prevalence, compound, formulation) duration (or
known micronutrient both)
deficiencies)
Supplementation
Better health.
Informed decisions.
Trusted evidence.
Abe 2016 MMNs Prevention Non-pregnant moth- Trial 1: 18 mg of iron (ferrous fu- Daily Duration: 6 Not reported
ers who exclusively fed marate), 15 mg of zinc (zinc oxide), 2 weeks to 15
Supplementa- breast milk or prac- mg of copper (cupric oxide), 162 mg weeks post-
tion with multi- ticed mixed feeding of calcium (calcium phosphate diba- partum
ple micronutri- sic), and other minerals and vitamins
ents for breast- Baseline anaemia sta-
feeding women tus/prevalence: not re- Trial 2: vitamin A 8000 IU, vitamin D
for improving ported 400 IU, vitamin E 30 IU, vitamin C 90
outcomes for mg, folic acid 0.8 mg, thiamin 1.7 mg,
the mother and Known MN deficien- riboflavin 2 mg, niacin 20 mg, vita-
baby cies: not reported min B6 4 mg, vitamin B12 8 μg, cal-
cium 200 mg, iodine 150 μg, iron 45
mg, and magnesium 100 mg
Houston 2018 Oral, IM or IV Preven- Adults (≥ 18 years) (age Oral iron: 16 mg/day to 200 mg/day Daily Duration: iron Adherence with
iron supple- tion/treat- range = 17 years to 55 IV iron: 200 mg/day to 1000 mg/day therapy was the trial inter-
Efficacy of iron mentation ment years); 15 trials includ- 46 days (mean vention was re-
supplementa- ed only women with IM: 100 mg per day = ± 30 days; ported in
tion on fatigue > 60% within this age range = 1 day 13 trials (RR
and physical ca- group to 112 days), 1.0, 95% CI 0.99
pacity in non- follow-up 57 to 1.01; 13 tri-
anaemic iron- Baseline anaemia sta- days (mean als, 958 partici-
deficient adults: tus/prevalence: non- = ± 24 days; pants)
a systematic anaemic range = 28
review of ran- days to 112

domised con- Known MN deficien-
days)
trolled trials cies: iron deficient
Lassi 2020 Iron folic acid Prevention Preconceptional Different dosages of iron and folic Daily (1 trial), Duration: Adherence was
supplemen- women of reproduc- acid: 60 mg elemental iron and 0.25 weekly (6 tri- 8 weeks to an outcome in
Effects of pre- tation versus tive age in low- and mg folic weekly (3 trials), 120 mg iron als), daily and more than 12 some trials, but
conception care placebo middle- income coun- and 3.5 mg folic acid (1 trial), 100 mg weekly (3 tri- weeks (1 tri- not results have
and pericon- tries (mean age not re- iron and folate 500 μg daily or week- als) al 8 weeks, been reported.
ception inter- ported) ly (1 trial), daily 60 mg elemental iron 2 trials 10
ventions on ma- and 0.5 mg folic acid (1 trial), week- weeks, 7 trials
ternal nutri- Baseline anaemia sta- ly 65 mg of elemental iron with 0.25 more than 12
tional status tus: not reported mg folic acid (1 trial), once daily or weeks)
111
(Review)
Table 12. Characteristics of interventions: non-pregnant women of reproductive age (aged 19 to 49 years) (Continued)
and birth out- Known MN deficien- weekly 350 mg iron and 1.5 mg folic
comes in low- cies: not reported acid (1 trail), daily or twice weekly 60
Library
Cochrane
and middle-in- mg iron and 0.5 mg folic acid (1 trial),
come countries: weekly 200 mg ferrous fumarate and
a systematic re- 200 mg folic acid (1 trial)
view
Low 2016 Oral iron Prevention Menstruating women Elemental iron dose: 1 mg/day to Daily (at least Duration: 1 Adherence was
alone or with (13 years to 45 years, 3 300 mg/day 5 days/week) week to 24 not reported
Better health.
Informed decisions.
Trusted evidence.
Daily iron sup- folic acid or trials included adoles- weeks in any form in
plementation vitamin C cent girls only) 33 trials = ferrous sulphate, 1 trial 34 of the trials.
for improv- =: ferrous sulphate and carbonyl Participants
ing anaemia, Baseline anaemia iron, 2 trials = carbonyl iron, 5 trials randomised to
iron status status/prevalence: = ferrous fumarate, 1 trial = ferric py- iron did not ap-
and health in anaemic and non- rophosphate and ferrous fumarate pear to have
menstruating anaemic participants together, remaining trials = variety of poorer adher-
women different iron formulations ence compared
Known MN deficien-
with those ran-
cies: iron deficiency re-
domised to
ported in some trials
placebo.
Sultan 2019 IV iron versus Treatment Postpartum women IV formulation: 300 mg to 600 mg fer- IV: alternate Start: with- Adherence as-
oral iron (age not reported); ric sucrose (9 trials), 1000 mg to 3000 days (5 tri- in 48 h after sessed in 10 tri-
Oral versus Hb upper cut-off val- mg ferric carboxy maltose (5 trials), als), consec- delivery (11 als, data report-
intravenous ues for inclusion: 8 g/ 1000 mg iron dextran (1 trial), 1200 utive days (4 trials), up to ed in 3. Two tri-
iron therapy dL (4 studies), 8.5 g/ mg iron maltoside (1 trial); oral iron: trials), weekly 10 days (2 trials reported
for postpar- dL (1 study), 9 g/dL 200 mg/day to 975 mg/day ferrous (3 trials), sin- als), not de- higher adher-
tum anemia: a (3 studies), 10 g/dL (5 sulphate (9 trials), ferrous ascorbate gle dose (2 tri- scribed (2 tri- ence in the IV
systematic re- studies), 10.5 g/dL (1 (2 trials), iron protein succinylate (2 als), not stat- als); duration: group (98% ver-
view and meta- study), postpartum trials), ferrous fumarate (1 trial), not ed (1 trial); 14 days to sus 84% and
analysis haemorrhage (1 study) described (1 trial) oral iron: daily 12 weeks (6- 100% versus
week trial pe- 84%) and 1 tri-
Known MN deficien- riod in 6 trials) al equal adher-
cies: not reported

ence in inter-
vention and
control group
(100%)
CI: confidence interval; Hb: haemoglobin; IM: intramuscular; IV: intravenous; MN: micronutrient; MMNs: multiple micronutrients; RR: risk ratio.
Table 13. Characteristics of interventions: pregnant women (aged 15 to 49 years)

Review Intervention Prevention Population (mean age, Dose (mean range) or com- Frequency Start of in- Adherence to
or treatment baseline anaemia sta- position or form of applica- tervention or intervention
112
(Review)
Table 13. Characteristics of interventions: pregnant women (aged 15 to 49 years) (Continued)
tus/prevalence, known mi- tion (including compound, duration (or
cronutrient deficiencies) formulation) both)
Library
Cochrane
Supplementation
Abu Hashim 2017 Bovine lacto- Treatment Pregnant women between 3 trials: bovine lactoferrin oral Once (1 trial) Start: second or Not reported
ferrin 12 and 36 weeks' gestation dose of 1 capsule of 100 mg, or twice (3 tri- third trimester
Lactoferrin or fer- twice a day before meals, for als) a day
rous salts for iron Baseline anaemia sta- 4 weeks Duration: 4
Better health.
Informed decisions.
Trusted evidence.
deficiency ane- tus/prevalence: mild IDA (di- weeks (3 trials)
mia in pregnan- agnosed in the second or 1 trial: bovine lactoferrin oral or 8 consecu-
cy: a meta-analy- third trimester according to dose of 1 capsule of 250 mg, tive weeks (1
sis of randomized the WHO (Hb < 11 g/dL)) daily, for 8 consecutive weeks trial)
trials
Known MN deficiencies: not
reported
Bhutta 2012 MMN Prevention Healthy pregnant women at MMN supplement formula At least 6 Start: 28 weeks' Not reported
any gestation UNIMMAP (30 mg iron, 400 μg days/week gestation at the
Is it time to re- folic acid, 15 mg zinc, 2 mg latest
place iron folate Baseline anaemia sta- copper, 65 μg selenium, 800
supplements tus/prevalence: not report- μg RE vitamin A, 1.4 mg vita- Duration: until
in pregnancy ed min B1, 1.4 mg vitamin B2, 18 delivery
with multiple mi- mg niacin, 1.9 mg vitamin B6,
cronutrients? Known MN deficiencies: not
2.6 μg vitamin B12, 70 mg vit-
reported
amin C, 5 μg vitamin D, 10 mg
vitamin E and 150 μg iodine)
or similar to UNIMMAP (small
variations in IFA)
Buppasiri 2015 Calcium sup- Prevention Pregnant women (any Various types of calcium: cal- Daily Start and dura- No data avail-
plementation trimester, most trials in cium carbonate, calcium glu- tion: 11 trials at able for com-
Calcium supple- second trimester; 3 trials conate, calcium lactate and 20 weeks’ ges- pliance
mentation (other

only adolescent pregnant combined (range = 1000 to tational age (or
than for prevent- women with mean age of 2000 mg/day; 3 trials < 1000 after) until de-
ing or treating hy- 17.0 years) mg/day (range = 300 mg to livery; 5 trials <
pertension) for 600 mg); 1 trial 600 mg at 22 20 weeks' ges-
improving preg- Baseline anaemia sta- to 32 weeks’ gestational age tational age
nancy and infant tus/prevalence: not report- and then 1200 mg from 32 until delivery;
outcomes ed weeks until delivery remaining trials
were unclear
reported
113
(Review)
Daru 2016 Iron (oral, in- Prevention Pregnant women at any Pregnant women with IDA: Pregnant Start: not speci- Not reported
cluding forti- and/or treat- gestation 200 mg IV iron (up to 400 mg) women with fied
Library
Cochrane
Systematic re- fied water, IV ment or 120 mg oral iron IDA: weekly
view of random- or IM) Baseline anaemia sta- Duration: until
ized trials of the tus/prevalence: IDA in 18 tri- Pregnant women with NAID: Pregnant 28 weeks' ges-
effect of iron sup- als 30 mg to 80 mg oral iron women with tation
plementation on NAID: weekly
iron stores and Known MN deficiencies: or daily
oxygen carrying NAID in 5 trials
Better health.
Informed decisions.
Trusted evidence.
capacity in preg-
nancy
Das 2018 LNS Prevention Pregnant women at 20 The energy content of LNS Daily The interven- Not reported
weeks' gestation or less was 118 kcal/day, LNS with tions began
Lipid-based nu- (mean age: 21.9 to 26.6 372 kcal/day during preg-
trient supple- years) nancy and last-
ments for mater- ed up to six
nal, birth, and in- Baseline anaemia status: months post-
fant developmen- not reported partum
tal outcomes
reported
De-Regil 2015 Periconcep- Prevention All women who became Folic acid supplementation Daily (2 to 3 Start and dura- Adherence re-
tional folate pregnant or were 12 or less doses ranged from 0.4 mg/ equal doses) tion: pericon- ported, but
Effects and safe- or folic acid week's pregnant at the time day to 4.0 mg/day ceptional peri- not further
ty of periconcep- supplementa- of the intervention od (supplemen- specified
tional oral folate tion alone or tation started
supplementation in combina- Baseline anaemia sta- before pregnan-
for preventing tion with oth- tus/prevalence: not report- cy and discon-
birth defects er vitamins or ed tinued after 12
minerals weeks of preg-
nancy)
reported

Govindappagari IV iron versus Treatment 11 trials: pregnant women IV iron: iron sucrose (8 trials), IV iron: in- Start: first Not reported
2019 oral iron with IDA (mean age: not FCM, LMW iron dextran fused in split trimester
reported); mean baseline doses every
Treatment of iron haemoglobin before treat- Oral iron: 100 mg to 200 mg other day Duration: at
deficiency ane- ment was < 8.0 g/dL in 5 elemental iron as ferrous sul- (maximum least 4 weeks
mia in pregnancy studies and > 8.0 g/dL in 6 phate (6 trials), ferrous fumer- daily dose of
with intravenous studies ate (3 trials), ferrous ascor- 200 mg, IV
versus oral iron: bate (1 trial), iron polymal- iron FCM at a
systematic re- Known MN: not reported tose complex (1 trial) dose of 1000
view and meta- mg once/
analysis week, LMW
114
(Review)
iron dextran
as a one-time,
Library
Cochrane
total dose in-
fusion)
Oral iron: dai-

ly
Haider 2011 MMN (at least Prevention Pregnant women (any ges- UNIMMAP (30 mg iron, 400 µg Daily Start: any ges- Missing com-
Better health.
Informed decisions.
Trusted evidence.
5 MNs, in- tation) folic acid, 15 mg zinc, 2 mg tation pliance data
Effect of multi- cluding the copper, 65 µg selenium, 800 in included
ple micronutrient UNIMMAP for- Baseline anaemia sta- µg RE vitamin A, 1.4 mg vita- Duration: any trials
supplementation mulation or tus/prevalence: not report- min B1, 1.4 mg vitamin B2, 18
during pregnancy those with ed mg niacin, 1.9 mg vitamin B6,
on maternal and comparable 2.6 µg vitamin B12, 70 mg vit-
birth outcomes Known MN deficiencies: not
composition) amin C, 5 µg vitamin D, 10 mg
reported
vitamin E and 150 µg iodine)
used in 12 trials, remaining
trials were comparable
to UNIMMAP except for a
small variation in dose of iron
and folic acid used
Haider 2013 Oral iron sup- Prevention Pregnant women (any ges- Oral iron or iron and folic Daily Start: early (< Not reported
plementation tation) acid, 10 mg to 240 mg daily (1 21 weeks' ges-
Anaemia, prena- (with or with- trial used a daily dose of 900 tation) in the
tal iron use, and out folic acid Baseline anaemia sta- mg) majority of tri-
risk of adverse or other MNs), tus/prevalence: not report- als, late (from
pregnancy out- iron fortifica- ed 22 weeks' ges-
comes: system- tion (2 trials) tation)
atic review and Known MN deficiencies: ID
meta-analysis reported in 1 trial Duration: 7 to
8 weeks (up to
30 weeks dur-

ing pregnancy)
Imdad 2012 Oral iron or Prevention Pregnant women (gesta- Iron: 20 mg/day to 300 mg/ Daily Start: no later Not reported
iron with folic tional age not reported) day than 28 weeks'
Routine iron/ acid gestation
folate supple- Baseline anaemia sta-
mentation dur- tus/prevalence: not report- Duration: not
ing pregnancy: ed specified
effect on mater-
nal anaemia and Known MN deficiencies: not
birth outcomes reported
115
(Review)
Keats 2019 MMN with Prevention Pregnant women (ranging Oral supplementation, com- Daily (1 trial Start: from en- Not reported
iron and folic from early pregnancy to 36 position of the MMN supple- 6 days/week, rolment (first,
Library
Cochrane
Multiple-mi- acid weeks' gestation) ment was different in all in- 1 trial twice/ second, or third
cronutrient sup- cluded trials (18 included iron week) trimester)
plementation for Baseline anaemia sta- and folic acid in the MMN sup-
women during tus/prevalence: anaemia at plement) Duration: until
pregnancy baseline reported in 2 trials delivery (11 tri-
als) or 4 (1 trial),
Known MN deficiencies: ID 6 (1 trial), 12 (5
Better health.
Informed decisions.
Trusted evidence.
reported in 1 trial and vita- trials), or 24 (2
min A deficiency reported in trials) weeks af-
2 trials ter delivery
Lassi 2013 Folic acid with Prevention Pregnant women (any age Most trials supplemented Daily Start: from 8 Not reported
or without and parity) women with folic acid in com- weeks' gesta-
Folic acid supple- iron or other bination with iron tion (most trials
mentation dur- vitamins and Baseline anaemia sta- from at least 20
ing pregnancy for minerals tus/prevalence: not report- Folic acid: 10 µg to 400 µg, weeks' gesta-
maternal health ed iron: 60 mg to 5 g tion)
and pregnancy
outcomes Known MN deficiencies: not Duration: dur-
reported ing pregnancy
McCauley 2015 Vitamin A Prevention Pregnant women (any ges- 1 trial: IM 600,000 IU vitamin A Daily or week- Start: from en- Complicane
alone or in tational age) palmitate in oil at parturition ly rolment assessed in
Vitamin A supple- combination only 1 trial
mentation dur- with other Baseline anaemia sta- 18 trials: 5750 IU to 444,000 IU Duration: 8-12
ing pregnancy supplements tus/prevalence: 2 trials in- vitamin A capsules weeks (up to 6
for maternal and cluded anaemic women weeks postpar-
newborn out- tum)
comes Known MN deficiencies: all
trials conducted in popula-
tions considered to be mod-
erately deficient in vitamin

A, 1 trial in women with se-
vere vitamin A deficiency, 2
trials (UK and USA) consid-
ered not deficient in vitamin
A
Peña-Rosas Daily iron (any Prevention Pregnant women (any ges- Dose range: 9 mg to 900 mg Daily Start: 12 weeks One third of
2015b supplements tational age) of elemental iron (18 trials 60 gestation (be- the trials re-
containing mg) fore 20 weeks in ported com-
Daily oral iron iron) Baseline anaemia sta- most trials, 13 pliance. Com-
supplementation tus/prevalence: 24 trials had trials that provided daily dose trials at or after pliance in the
during pregnancy non-anaemic women; the of folic acid: 0.01 mg to 5 mg
116
iron and con-

(Review)
remaining trials were un- 13 trials: ferrous sulphate; 6 20 weeks' ges- trol groups
clear but may have included trials: ferrous fumarate; 1 tri- tation) seemed to be
Library
Cochrane
women with mild or moder- al: ferrous iron; 6 trials: fer- similar.
ate anaemia rous gluconate; the remaining Duration: un-
trials: ferrous betainate hy- til delivery (or
Known MN deficiencies: not drochloride, heme iron from postpartum)
reported porcine blood, ferritin in a mi-
cro granulated gastric resis-
tant capsule, chelated iron
Better health.
Informed decisions.
Trusted evidence.
aminoates, iron EDTA
Peña-Rosas Intermittent Prevention Pregnant women (any ges- Dose range: 80 mg to 300 Weekly (on Start: before 20 Reported
2015a iron (with or tational age) mg elemental iron per week 1 day each weeks' gesta- in some tri-
without other (dose in the daily supple- week) tion (9 trials); als, but not
Intermittent oral vitamins and Baseline anaemia sta- mentation comparison group in the remain- further de-
iron supplemen- minerals) tus/prevalence: 9 trials had ranged from 40 mg to 120 mg ing trials, ges- scribed
tation during non-anaemic women; 1 tri- elemental iron daily) tational age at
pregnancy al had women who were the start of sup-
anaemic at baseline; the re- In trials with folic acid: 0.4 plementation
maining trials may have in- mg/week to 3.5 mg/week was mixed or
cluded some women with unclear
moderate or mild anaemia
at baseline Duration: at
least 10 weeks
Known MN deficiencies: not (some trials un-
reported til delivery)
Qassim 2018 IV IPM, IS and Treatment IS (2635 pregnant women; IV IPM, IS, or FCM Daily Start of inter- Not reported
FCM 41 studies), FCM (276 preg- vention: any
Safety and effica- nant women; 4 studies) and gestational
cy of intravenous IPM (164 pregnant women; weeks
iron polymaltose, 3 studies)
iron sucrose and

ferric carboxy- Known MN deficiencies: not
maltose in preg- reported
nancy: a system-
atic review
Qassim 2019 IV iron thera- Treatment Pregnant women who ini- IV IPM, IS, or FCM Daily Start of inter- Not reported
py tially had low haemoglobin vention: 22 to
Intravenous or levels (< 110 g/L) or were at 33.3 gestational
oral iron for treat- high risk of developing IDA weeks
ing iron deficien-
cy anaemia dur- Baseline mean haemoglo-
ing pregnancy: bin levels (range, 60 g/L to
117
systematic re- 109 g/L) and mean gesta-

(Review)
view and meta- tion at enrolment (range, 22
analysis to 33.3 weeks);
Library
Cochrane
reported
Radhika 2019 Parenteral Treatment 18 studies (1633 antenatal IV IS versus oral iron (ferrous Daily Antenatal and Not reported
iron (IV IS) women) and 8 studies (713 sulphate, ferrous ascorbate or post-partum
Parenteral versus post-partum women) fumarate) period
Better health.
Informed decisions.
Trusted evidence.
oral iron for treat-
ment of iron defi- Known MN deficiencies: not
ciency anaemia reported
during pregnancy
and post-partum:
a systematic re-
view
Reveiz 2011 Any iron in- Treatment Pregnant women (any ges- Oral iron: 20 mg to 300 mg Oral iron: dai- Start: between Compliance
tervention tational age) ly or weekly 16 to 20, 26 and reported in
Treatments for (oral, oral iron IM iron: total dose of iron (mg) 34 weeks' ges- 1 trial com-
iron-deficiency plus adjuncts, Baseline anaemia sta- = weight (kg) x Hb deficit (g/ IM iron: alter- tation paring oral
anaemia in preg- IM, IV, blood tus/prevalence and known dL) x 4.4 + 500, 2 injections of nate days iron polymal-
nancy transfusion, micronutrient deficiencies: 250 mg elemental iron Duration: 4 to tose complex
pregnant women with a di- IV iron: every 16 weeks (oral
recombinant versus fer-
agnosis of anaemia attrib- IV iron: weight in kg x (target other day, iron up to deliv-
erythropoi- rous sulphate;
uted to ID Hb - actual Hb) x 0.25 + 500 twice weekly ery)
etin) found no evi-
(maximum total dose 200 mg
dence of a dif-
to 300 mg or 500 mg elemen-
ference
tal iron)
Rumbold 2015 Vitamin C Prevention All pregnant women of any 12 trials: vitamin C alone Daily Start: in the sec- Not reported
supplementa- gestation (9 trials recruited 15 trials: vitamin C in addition ond trimester
Vitamin C sup- tion women who were at “high” to vitamin E, or vitamin C and
plementation in or “increased” risk of pre- vitamin E in addition to allop- Duration: not

pregnancy eclampsia, 2 trials includ- urinol, or aspirin and fish oil reported in
ed women with established 6 trials: additional supple- many trials
pre-eclampsia) ments containing iron, folic
acid, vitamin B and/or cal-
Baseline anaemia sta- cium or a “standard prena-
tus/prevalence: not report- tal vitamin” were given to all
ed women (i.e. in the vitamin C
group and the control group)
Known MN deficiencies: 1
The most common daily
trial had women at high risk
dosage of vitamin C was 1000
of ID, and 1 trial had 11 par-
mg/day (15 trials), 500 mg/
ticipants with vitamin C de-
day (6 trials), 100 mg/day (4
118
ficiency
(Review)
trials), 2000 mg/day (2 trials),
400 mg (1 trial), and 250 mg/
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Cochrane
day for 6 days and thereafter
250 mg/week (vaginally, 1 tri-
al)
Shi 2015 IV iron su- Treatment Pregnant women (gesta- IV iron sucrose total dose IV: every other Start: not speci- Not reported
crose tional age = not reported) from formula: weight × (11 or day fied
Intravenous iron 12 g/dL – actual Hb) × 0.24 +
Better health.
Informed decisions.
Trusted evidence.
sucrose versus Baseline anaemia sta- 500 mg Oral iron: dai- Duration: 4 to 6
oral iron in the tus/prevalence: diagnosed ly weeks
treatment of IDA Oral elemental iron: 100 mg
pregnancy with to 300 mg daily (as ferrous
iron deficiency Known MN deficiencies: not sulphate, iron polymaltose
anaemia: a sys- reported complex or ferrous fumerate)
tematic review
Thorne-Lyman Supplemen- Prevention Pregnant women (any ges- Dose: vitamin A 3333 IU to 10 11 trials: dai- Duration: no Not reported
2012 tation with and treat- tational age) 000 IU per day (2 trials with ly; 4 trials: description
vitamin A or ment HIV-positive women: vitamin weekly; 2 tri-
Vitamin A and carotenoids, Baseline anaemia sta- A 5000 IU per day and 30 mg als: unclear Start: between
carotenoids dur- or both tus/prevalence: 3 trials in- beta-carotene as well as a 12 to 39 weeks'
ing pregnancy cluded anaemic women, 3 200,000 IU dose of vitamin A gestation
and maternal, trials included anaemic and at delivery)
neonatal and in- non-anaemic
fant health out-
comes: a system- Known MN deficiencies: not
atic review and reported
meta-analysis
Fortification
Suchdev 2015 MNP for Prevention Pregnant women (any ges- Trial 1: MNP (60 mg of ele- Trial 1: daily Start: 14 to 22 Maternal ad-
point-of-use tation and parity) mental iron as ferrous fu- weeks' gesta- herence re-

Multiple micronu- fortification marate, 400 μg of folic acid, Trial 2: daily tion (trial 1), be- ported in 1 tri-
trient powders of semi-sol- Baseline anaemia sta- 30 mg of vitamin C, and 5 mg for 6 months fore 24 weeks' al (MNP ver-
for home (point- id foods con- tus/prevalence: not report- of zinc) versus 60 mg elemen- then weekly gestation (trial sus iron or
of-use) fortifica- taining at ed, but women with severe tal iron and 400 μg folic acid 2) folic acid sup-
tion of foods in least 3 MMNs, anaemia were excluded plement): RR
pregnant women with 1 of them Trial 2: MNP (15 mg elemen- Duration: until 0.76, 95% CI
Known MN deficiencies: not tal iron, 400 μg folic acid and 32 weeks' ges-
being iron 0.66 to 0.87
reported 5 additional micronutrients tation (trial 1),
(zinc, iodine, vitamin E, vita- until 3 months
min C, vitamin B12) versus 1 postpartum (tri-
tablet (15 mg elemental iron, al 2)
119
(Review)
400 μg folic acid and the same
5 additional MNs)
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Cochrane
CI: confidence interval; EDTA: ethylenediaminetetraacetate; FCM: ferric carboxy maltose; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; IFA: iron or folic
acid; IM: intramuscular; IPM: iron polymaltose; IV: intravenous; IS: iron sucrose; LMW: low molecular weight; LNS: lipid-based nutrient supplementation; MN: micronutrient;
MNP: micronutrient powder; NAID: non-anaemic iron deficiency; RR: risk ratio; UNIMMAP: United Nations International Multiple Micronutrient Preparation; WHO: World Health
Organization.
Better health.
Informed decisions.
Trusted evidence.
Table 14. Characteristics of interventions: mixed populations
or treatment line anaemia status/preva- composition or form of tervention or intervention
lence, known micronutrient de- application (including duration, or
ficiencies) compound, formulation) both
Supplementation
Arabi 2020 Oral vitamin D Prevention 14 trials: participants aged 17.5 Vitamin D fortified food Daily Duration: 3 Not reported
supplements and treat- to 68 years old (including RCTs with cholecalciferol (4 tri- hours to 36
The effect of vita- ment with healthy adults, anaemic als), oral vitamin D (chole- months
min D supplemen- patients, chronic kidney dis- calciferol) supplements
tation on hemoglo- ease patients, heart failure pa- (8 trials), supplemented
bin concentration: tients, hypertensive patients, with ergocalciferol (1 tri-
a systematic review critically ill patients and ath- al), with calcitriol (1 trial).
and meta-analysis letes) The minimum vitamin
D dosage was 20 IU and
Baseline anaemia status: not maximum was 500,000 IU.
reported

ported

Basutkar 2019 Vitamin D Treatment Patients with iron deficiency Vitamin D and calcium Daily Duration: 12 Not reported
supplementa- anemia (20 to 45 years) containing snack bar, 10 (3 months) to
Vitamin D supple- tion Known MN deficiencies: not re- mcg and 25 mcg of Vita- 16 weeks
mentation in pa- ported min D, iron plus vitamin D
tients with iron de- supplementation
ficiency anaemia: A
systematic review
and a meta-analy-
sis
Casgrain 2012 Oral iron, for- Prevention Healthy adults (≥ 18 years) Iron supplementation: 5 Daily or week- Duration: 3 to Not reported
tified food, mg to 240 mg as iron fu- ly 24 weeks
120
(Review)
Table 14. Characteristics of interventions: mixed populations (Continued)
Effect of iron intake or rich nat- Baseline anaemia status/preva- marate, ferrous sulphate
on iron status: a ural dietary lence: anaemic and non- (mainly), ferric polymal-
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Cochrane
systematic review sources anaemic tose
and meta-analysis
of randomized con- Know micronutrient deficien- Fortification with iron:
trolled trials cies: any baseline iron status 1.42 mg to 27.9 mg (forti-
(iron deficient in many trials) fied wheat-based snacks,
rice, food bar, fish sauce)
Better health.
Informed decisions.
Trusted evidence.
Gera 2007a Oral iron, par- Prevention Children (0 to 19 years, no age Iron: 5 mg to 120 mg/day Daily Duration: 1 Most of the in-
enteral route group dominated, i.e. > 60%) or 1 mg/kg/day to 4 mg/ week to 12 cluded trials
Effect of iron sup- or as formu- kg/day (compound not re- 2 trials: week- months do not pro-
plementation on la, milk, or ce- Baseline anaemia status/preva- ported) ly vide relevant
haemoglobin re- reals fortified lence: anaemic and non- compliance
sponse in children: with iron anaemic (mean baseline Hb < data.
systematic review 11 g/dL in 37 analytic compo-
of randomised con- nents, Hb ≥ 11 in 54 analytic
trolled trials components)
Know MN deficiencies: iron de-

ficiency
Gera 2009 Oral iron in Prevention Children (0 to 18 years, no age Iron: 5 mg to 60 mg per Daily to once Duration: 3 Not reported
combina- group dominated, i.e. > 60%) day (compound not re- a week weeks to 12
Effect of combining tion with 2 or ported) months
multiple micronu- more MNs Baseline anaemia status/preva-
trients with iron lence: anaemic and non-
supplementation anaemic (mean baseline Hb <
on Hb response in 11 g/dL in 15 analytic compo-
children: system- nents, Hb ≥ 11 in 18 analytic
atic review of ran- components)
domized controlled
trials Know MN deficiencies: yes, but
not specified

Silva Neto 2019 Iron supple- 3 trials: pre- 6 trials infants and children Dietary plan (4 trials) or Daily (at least Not reported Not reported
mentation vention, 6 (age = 0.25 years to 7.3 years, fortified food (8 trials): 5 times per
Effects of iron sup- versus dietary trials: treat- males and females) iron dose = 7 mg to 35.4 week)
plementation ver- intervention ment, 3 trials: mg
sus dietary iron on (fortification N/A 5 trials: adults (mean age = 18.5
the nutritional iron or dietary to 29 years, females) Iron supplementation: 2.5
status: Systematic plan) mg to 105 mg
review with meta- 1 trial: pregnant women (mean
analysis of ran- age = 25 years)
domized controlled
Baseline anaemia status/preva-
trials
lence: iron deficiency anaemia
121
(Review)
(6 trials = yes, 3 trials = no, 3 tri-
als = no information)
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Known MN deficiencies: iron
deficiency
Smelt 2018 Vitamin B12 or Prevention Older people (60.3 to 80 years) Vitamin B12 (0.01 mg to 1 6 trials: daily Duration: 4 Not reported
folic acid sup- mg) or folic acid (0.8 mg to weeks to 3
The effect of vita- plementation Baseline anaemia status/preva- 5 mg) supplementation, 1 trial: weekly years
Better health.
Informed decisions.
Trusted evidence.
min B12 and folic lence: number of individuals including tablet, capsule
acid supplemen- with anaemia was small and intramuscular
tation on routine
haematological pa- Know MN deficiencies: vitamin
rameters in older B12 deficiency and folate defi-
people: an individ- ciency in some trials
ual participant da-
ta meta-analysis
Tay 2015 Oral iron Prevention Elderly people after hip or Ferrous sulphate 200 mg 2 trials: 3 Duration: 4 1 trial report-
knee arthroplasty (mean age times daily weeks to 6 ed poor com-
Systematic review range = 70 to 83 years, men and weeks pliance.
and meta-analy- women) 1 trial: twice
sis: what is the evi- daily Start of inter-
dence for oral iron Baseline anaemia status/preva- vention for el-
supplementation lence: participants were derly people:
in treating anaemia anaemic after surgery, but after hip or
in elderly people? none of the participants were knee arthro-
anaemic on admission plasty

ported
Tolkien 2015 Oral ferrous Prevention Oral iron versus placebo (20 tri- Oral iron versus placebo: Daily Duration oral Not reported
sulphate and treat- als, 3168 participants): adults, oral dose 20 mg/Fe/day to iron versus

Ferrous sulfate ment including pregnant women (18 222 mg/Fe/day placebo: 1 to
supplementa- to 58.6 years), baseline Hb sta- 26 weeks
tion causes signifi- tus in 12 trials = 10.4 g/dL to Oral iron versus IV iron:
cant gastrointesti- 15.25 g/dL (not reported for the oral dose 100 mg/Fe/day Duration oral
nal side-effects in remaining trials), 19 trials in to 400 mg/Fe/day (ferrous iron versus IV
adults: a systemat- healthy non-anaemic individ- sulphate) iron: 4 to 26
ic review and meta- uals, 1 trial in anaemic partici- weeks
analysis pants
Oral iron versus IV iron (23 tri-

als, 3663 participants): adults,
including pregnant women (15
122
(Review)
to 66 years), baseline Hb status
= 7.6 g/dL to 12.4 g/dL
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Cochrane
ported
Fortification
Das 2019b Multiple mi- Prevention 36 trials: children (29 trials: MMN fortification (3 or Daily or week- Duration: 8 Not reported
Better health.
Informed decisions.
Trusted evidence.
cronutrient preschool and school-aged chil- more MNs) by any food ve- ly weeks to 1
Food fortification (MMN) forti- dren, 4 trials: infants, 3 trials: hicle: rice and flour (12 tri- year; 29 tri-
with multiple mi- fication (3 or children aged 1 to 3 years) als), dairy products (9 trials: less than
cronutrients: im- more MNs) by als), non-dairy beverages 6 months,
pact on health out- any food vehi- 3 trials: pregnant women (13 trials), biscuits (6 tri- 14 trials:
comes in general cle als), salt (2 trials) between 6
population 3 trials: adults
months and 1
1 trial: elderly population over year
70 years old mean age: not re-
ported
Baseline anaemia status: not

reported
Known micronutrient deficien-

cies: not reported
Field 2020 Fortifica- Prevention 9 trials: 6 trials included chil- Any form of wheat flour Daily 3 to 8 months Adherence
tion of wheat dren aged 6 to 11 years, 1 trial iron fortification indepen- (8 trials) was
Wheat flour fortifi- flour with iron included children aged 6 to 12 dent of length of inter- measured in
cation with iron for alone or in years, 1 trial included children vention, extraction rate 24 months (1 some studies
reducing anaemia combination aged 6 to 13 years, and 2 trials of wheat flour, iron com- trial) through 24-
and improving iron with other mi- included children aged 6 to 15 pounds used, prepara- hour recalls
status in popula- cronutrients years old. Another trial includ- tion of the iron-flour pre- and in some
tions

ed children aged 9 months to mix, and fortification lev- cases weigh-
11 years, primary school chil- els achieved in the wheat ing of food re-
dren aged 6 to 11 years, and flour or derivative foods mains in the
non-pregnant women. 2 trials meals.
included adult women. One Iron compounds: NaFeED-
trial targeted adolescent girls TA ferrous sulphate, el-
aged 15.2 ± 2.4 years emental iron, ferrous fu-
marate
Baseline anaemia status: var-
ied; low (< 20%) in 2 trials, mod- Amount of elemental iron
erate in 4 trials, high in 2 tri- added to flour: 41 mg
als, 1 trial did not specify preva- iron/kg to 60 mg iron/kg
flour (3 trials), < 40 mg
123
lence
(Review)
Known MN deficiencies: not re- iron/kg flour (2 trials), > 60
ported mg iron/kg flour (2 trials),
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Cochrane
80 mg/kg for electrolytic
iron and reduced iron
and 40 mg/kg for ferrous
fumarate (1 trial), un-
known (1 trial)
Finkelstein 2019 Iron-biofor- Prevention 1 trial: male and female adoles- Crop: rice, pearl millet, Daily Duration: 4 to Not reported
Better health.
Informed decisions.
Trusted evidence.
tified staple cents aged 12 to 16 years old beans 9 months
Iron biofortifica- crops
tion interventions 2 trials: adults females (18 to 45 Iron content: 10 mg/kg
to improve iron sta- years) to 86 mg/kg dry per crop,
tus and functional iron intake from staple 1.8
outcomes Baseline anaemia status: 28% mg/d to 17.6 mg/d
to 37% anaemic at baseline
Percentage of total di-
Known MN deficiencies: 34% to etary iron: 18% to 90%
86% to iron deficient at base-
line
Garcia-Casal 2018 Maize flour or Prevention General population older than 3 trials: 2.8 mg to 5.6 mg Not specified Duration: 6 to Not reported
maize flour 2 years of age without critical elemental iron per 100 g 10 months
Fortification of products for- illness or severe comorbidi- maize flour
maize flour with tified with ties (children = 6 months to 14
iron for controlling iron plus oth- years, adolescents = 10 to 19 1 trial: 9.8 mg reduced
anaemia and iron er vitamins years, women = 20 to 49 years) iron per 100 g flour
deficiency in popu- and miner-
lations Baseline anaemia status/preva- 1 trial: 42.4 mg ferrous fu-
als versus
lence: < 20% in 3 trials, > 40% in marate per 100 g maize
unfortified
1 trial and not reported in 1 trial flour
maize flours
or maize flour
Know MN deficiencies: all tri-
products
als conducted in settings with a

high prevalence of MN deficien-
cies, especially iron
Gera 2012 Iron food for- Prevention Apparently healthy (non-dis- Computed additional iron Daily in 50 an- Duration: up Compliance
tification or eased) individuals, families, or intake: ≤ 10 mg in 49 trials alytic compo- to 7 months directly ob-
Effect of iron-for- biofortifica- communities (63%) and > 10 mg in 29 nents, inter- in 44 trials served: 21 an-
tified foods on tion trials (37%) mittent in 35 (51%), 7 to alytic compo-
hematologic and Baseline anaemic status/preva- 12 months nents versus
biological out- lence: Hb concentration ≤ 120 Cereal-based fortification in 30 trials 56 others
comes: systematic g/L in 49 of 80 (57%) analytic (36 trials; 42%): salt (12 tri- (35%), and 12
review of random- components als; 14%), sauces (fish and months in 11
ized controlled tri- soy; 9 trials; 11%), and (13%) trials
124
als milk (9 trials; 11%)

(Review)
Known MN deficiencies: iron Ferrous sulphate (24 tri-
deficiency (serum ferritin was ≤ als; 28%), NaFeEDTA (17
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20 μg/L in 22 of 47 (47%)) trials; 20%), electrolytic
iron (11 trials; 13%), ferric
pyrophosphate (7 trials;
8%), hydrogen-reduced
iron (3 trials; 3%), and
heme (3 trials; 3%) or fer-
ric orthophosphate (3 tri-
Better health.
Informed decisions.
Trusted evidence.
als; 3%), ferrous fumarate
(6 trials; 7%), amino acid
chelates (2 trials; 2%), iron
gluconate (1 trial; 1%), or
ammonium citrate (1 trial;
1%)
Hess 2016 MN (iron, vit- Prevention Children and adults from 5 to Salt: 1 mg to 2 mg iron/g Not specified Duration: fol- Adherence to
amins, zinc, 50 years salt; masala powder: 25 low-up mostly intervention
Micronutrient for- iodine, fo- μg NaFeEDTA/g masala; under 1 year was not re-
tified condiments late, calcium, Baseline anaemia status/preva- soy sauce: 0.3 mg to 4 mg (range = 2.4 ported in in-
and noodles to re- phosphorus, lence: anaemia rate at baseline NaFeEDTA/mL soy sauce; months to 2 cluded trials
duce anemia in magnesium, 46% noodles: 20.6 mg NaFeED- years)
children and adults selenium) for- TA/100 g noodles; fish
—a literature re- Known MN deficiencies: not re-
tified condi- sauce: 1 mg Fe/mL fish
view and meta- ported
ments or noo- sauce
analysis dles product
Huo 2015 NaFeED- Prevention Any population in which Iron in NaFeEDTA ranged Daily Duration: 3 to Not reported
TA-fortified anaemia is a public health from 2.3 to 20 mg/day/ 18 months
Effect of NaFeED- soy sauce problem (Chinese, aged 3 to 55 person, iron dosages were
TA-fortified soy (prevention) years, 3- to 6-year-old children, < 4 mg/day in 8 trials and
sauce on anemia 9 trials focusing on teenagers, ≥ 4 mg/day in 7 trials
prevalence in Chi- 3 trials on pregnant women,

na: a systematic and 1 trial covered all groups of
review and meta- children > 3 years)
analysis of ran-
domized controlled Baseline anaemia status/preva-
trials lence: anaemic and non-
anaemic
Known MN deficiencies: iron

deficiency
Peña-Rosas 2019 Rice forti- Treatment or Population older than 2 years Rice fortified with ele- Daily Duration: 2 Not reported
fied with iron prevention of age, including pregnant mental iron, vitamin A, weeks to 4
125
alone or in women zinc, folic acid, thiamin, years

(Review)
Fortification of rice combination Baseline anaemia status: 5% riboflavin, niacin, pyri-
with vitamins and with other to 62% in children, 21% in doxine, cobalamin. The
Library
Cochrane
minerals for ad- MNs women, and 34% in teenagers amount of elemental iron
dressing micronu- Rice fortified per 100 g of rice ranged
trient malnutrition with vitamin Known MN deficiencies: not re- from 0.2 mg to 112.8 mg;
A alone or in ported vitamin A: 0.15 mg to 2.1
combination mg; zinc: 2 mg to 18 mg;
with other ferrous sulphate: 18 mg/g
MNs
Better health.
Informed decisions.
Trusted evidence.
Ramírez-Luzuriaga DFS Prevention Any participants (subgroup Most trials used concen- Not specified Duration: Not reported
2018 analysis for children aged < 5 trations of 1 mg to 3 mg el- mostly > 6
years, school-aged children, emental Fe/g salt months
Impact of dou- non-pregnant, non-lactating The 3 main iron sources
ble-fortified salt women of childbearing age, used for salt fortification
with iron and io- men, pregnant women) were ferrous sulphate, fer-
dine on hemoglo- rous fumarate and ferric
bin, anemia, and Baseline anaemia status/preva- pyrophosphate
iron deficiency ane- lence: not reported
mia: a systematic
review and meta- Known MN deficiencies: not re-
analysis ported
Sadighi 2019 Fortification Prevention 19 trials of infants/toddlers (4 Fortification vehicles: 61 Not specified Mean dura- Not reported
of flour (e.g. to 36 months), 42 of children (3 trials wheat flour, maize tion: 20.6
Systematic review wheat,maize, to 19 years), 31 of women (15 to flour in 7 trials, wheat and months (SD:
and meta-analy- or rice), either 49 years), and 2 of people of all maize flours in 7 trials, 25.5, range: 2
sis of the effect of in a raw form ages rice flour in 4 trials, wheat to 144)
iron-fortified flour or in a cook- and corn flours in 4 tri-
on iron status of ing process, Baseline anaemia status/preva- als, maize and soy flours
populations world- with iron or lence: not reported in 2 trials, corn flour in 1
wide with iron and trial, maize, beans, bam-
other MNs bara nuts, and groundnuts
ported
flours in 1 trial, rice and

soybeans flours in 1 trial,
rye flour in 1 trial, wheat
and soybean flours in 1 tri-
al, and unknown flour in
4 trials; iron alone added
to flour: 31 trials, iron with
other micronutrients: 63
trials
126
(Review)
Tablante 2019 Wheat flour Prevention Male and female children (5 to Wheat flour chapattis Daily Duration: over Not reported
fortified with 12 years) (cluster-RCT reported were fortified with 0.15 a six-month
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Fortification of folic acid plus relevant outcomes: Bangladesh mg of folic acid per 100 g period
wheat and maize other vita- has had more than a 75% de- of flour (1.5 ppm), along
flour with folic mins and min- crease in the incidence of with other MNs (clus-
acid for population erals malaria cases between 2000 ter-RCT reported relevant
health outcomes and 2014) outcomes)
Better health.
Informed decisions.
Trusted evidence.
Yadav 2019 DFS (iron and Prevention Children 1 to 5 years (1 study), 1 mg/g salt ferrous sulfate Not specified Duration: 6 to Not reported
iodine) versus school children 5 to 18 years (3 trials), 2 mg/g to 3 mg/g 18 months
Meta-analysis of ef- iodine only IS (6 studies), non-pregnant and salt ferric pyrophosphate
ficacy of iron and non-lactating females 15 to 45 (3 trials), 1 mg/g to 2 mg/
iodine fortified salt years (1 study), healthy and g salt ferrous fumarate (4
in improving iron nonpregnant females 18 to 55 trials)
nutrition status years (1 study), male and fe-
male participants 10 to 65 years
(1 study)
Baseline anaemia status/preva-

lence: not reported

ported
Geerligs 2003 Consumption Prevention People in developing coun- Use of iron or aluminium Daily Duration: 5 to Daily compli-
or use of food tries (minimum age was set at 4 pots 12 months ance reported
Food prepared prepared in months) in 3 trials
in iron cooking iron or alu-
pots as an inter- minium pot Baseline anaemia status/preva- Trial 1: initial
vention for reduc- lence: high prevalence of 10 weeks of
ing iron deficiency anaemia iron pot use

anaemia in devel- 80% to 85%,
oping countries: a Known MN deficiencies: high subsequent
systematic review prevalence of iron deficiency 10 weeks 68%
to 70%
Trial 2: 2 of
22 people
stopped using
iron pots after
4 to 5 months
Trial 3: iron
pot use 34.7%
127
(Review)
after 3 weeks,
and 31.1% af-
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ter 20 weeks
DFS: double‑fortified salt; IDA: iron deficiency anaemia; IS: iodine-fortified salt; MN: micronutrient; MMNs: multiple micronutrients; NaFeEDTA: sodium iron
ethylenediaminetetraacetate; SD: standard deviation.
Better health.
Informed decisions.
Trusted evidence.
Table 15. AMSTAR ratings for each systematic review: infants (aged 6 to 23 months)
Study and review title 1.* 2.* 3.* 4.* 5.* 6.* 7.* 8.* 9.* 10.* 11.* Total
score
(out of
a maxi-
mum of
11)
Supplementation
Abdullah 2013 No Yes Yes No Yes Yes Yes No Yes Yes No 7
Efficacy of oral iron ther-

apy in improving the de-
velopmental outcome of
pre-school children with
non-anaemic iron defi-
ciency: a systematic re-
view
Das 2019a Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
Preventive lipid-based
nutrient supplements

given with complemen-
tary foods to infants
and young children 6
to 23 months of age for
health, nutrition, and
developmental out-
comes
Dekker 2010 No Yes Yes Yes No Yes Yes No Yes No No 6
Zinc supplementation
in children is not associ-
128
(Review)
Table 15. AMSTAR ratings for each systematic review: infants (aged 6 to 23 months) (Continued)
ated with decreases in
hemoglobin concentra-
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tions
Pasricha 2013 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
Effect of daily iron sup-

plementation on health
in children aged 4-23
Better health.
Informed decisions.
Trusted evidence.
months: a systematic
review and meta-analy-
sis of randomised con-
trolled trials
Petry 2016b No Cannot Yes No No No Yes Yes Yes Yes No 5

answer
The effect of low dose
iron and zinc intake on
child micronutrient sta-
tus and development
during the first 1000
days of life: a systematic
sis
Pratt 2015 No No Yes No No Yes Yes No Yes No No 4
A review of the strate-

gies used to reduce the
prevalence of iron defi-
ciency and iron deficien-
cy anaemia in infants
aged 6-36 months

Fortification
Dewey 2009 No Yes No No No Yes Yes No Yes Yes No 5
Systematic review and

meta-analysis of home
fortification of comple-
mentary foods
Eichler 2012 Yes No Yes No No Yes Yes No Yes No No 5

129
(Review)
Effects of micronutrient
fortified milk and cere-
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Cochrane
al food for infants and
children: a systematic
review
Matsuyama 2017 No Yes Yes No No Yes Yes No Yes Yes No 6
Effect of fortified milk on
Better health.
Informed decisions.
Trusted evidence.
growth and nutritional
status in young children:
a systematic review and
meta-analysis
Salam 2013 No Yes Yes Yes No Yes Yes No No No No 5
Effectiveness of mi-
cronutrient powders
(MNP) in women and
children
Suchdev 2020 Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes 10
Home fortification of
foods with multiple mi-
cronutrient powders for
health and nutrition in
children under two years
of age
Kristjansson 2015 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11

Food supplementation
for improving the phys-
ical and psychosocial
health of socio-econom-
ically disadvantaged
children aged three
months to five years
Shapiro 2019 Yes Yes Yes Yes No Yes Yes No Yes No No 7
A systematic review in-

vestigating the relation
130
(Review)
between animal-source
food consumption and
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Cochrane
stunting in children aged
6-60 months in low and
middle-income coun-
tries
AMSTAR: A Measurement Tool to Assess Reviews
Better health.
Informed decisions.
Trusted evidence.
*Criteria for AMSTAR:
1. A priori design provided
2. Duplicate study selection and data extraction
3. Comprehensive literature search performed
4. Status of publication used as an inclusion criterion
5. List of studies (included and excluded) provided
6. Characteristics of included studies provided
7. Quality of included studies assessed and documented
8. Quality of included studies used appropriately in formulating conclusions
9. Appropriate methods used to combine the findings of the studies
10. Likelihood of publication bias assessed
11. Conflict of interest stated
Table 16. AMSTAR ratings for each systematic review: preschool and school-aged children (aged 2 to 10 years)
score
(out of
a maxi-
mum of
11)
Supplementation

Low 2013 Yes Yes Yes Yes No Yes Yes No Yes Yes No 8
Effects of daily iron sup-

plementation in prima-
ry-school-aged children:
systematic review and
meta-analysis of ran-
domized controlled tri-
als
131
De-Regil 2011 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
(Review)
Table 16. AMSTAR ratings for each systematic review: preschool and school-aged children (aged 2 to 10 years) (Continued)
Intermittent iron supple-
mentation for improving
Library
Cochrane
nutrition and develop-
ment in children under
12 years of age
Mayo-Wilson 2014a Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
Zinc supplementation
Better health.
Informed decisions.
Trusted evidence.
for preventing mortality,
morbidity, and growth
failure in children aged
6 months to 12 years of
age
Thompson 2013 Yes Cannot Yes Cannot No Yes Yes Yes Yes Yes No 7
answer answer
Effects of daily iron sup-
plementation in 2- to
5-year-old children:
meta-analysis
Fortification
Aaron 2015 No Yes No No No Yes Yes No Yes Yes No 5
Multiple-micronutrient
fortified non-dairy bev-
erage interventions re-
duce the risk of anemia
and iron deficiency in
school-aged children
in low-middle income

countries: a systematic
sis
Das 2013a No Yes Yes Yes No Yes Yes No Yes No No 6
Systematic review of
zinc fortification trials
De-Regil 2017 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
132
(Review)
Table 16. AMSTAR ratings for each systematic review: preschool and school-aged children (aged 2 to 10 years) (Continued)
Point-of-use fortification
of foods with micronu-
Library
Cochrane
trient powders contain-
ing iron in children of
preschool and school
age
Eichler 2019 Yes Yes No Yes Yes Yes Yes No Yes Yes No 8
Better health.
Informed decisions.
Trusted evidence.
Health effects of mi-
cronutrient fortified
dairy products and cere-
al food for children and
adolescents: a systemat-
ic review

Table 17. AMSTAR ratings for each systematic review: adolescent children (aged 11 to 18 years)

score
(out of
a maxi-
mum of
11)
Supplementation
Fernández-Gaxiola 2019 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
133
(Review)
Table 17. AMSTAR ratings for each systematic review: adolescent children (aged 11 to 18 years) (Continued)
Intermittent iron sup-
plementation for reduc-
Library
Cochrane
ing anaemia and its as-
sociated impairments
in adolescent and adult
menstruating women
Neuberger 2016 Yes Yes Yes No Yes Yes Yes Yes Yes Yes No 9
Better health.
Informed decisions.
Trusted evidence.
Oral iron supplements
for children in malar-
ia-endemic areas
Salam 2016 No Yes Yes No No Yes Yes Yes Yes No No 6
Interventions to improve
adolescent nutrition: a
meta-analysis
Salam 2020 Yes Yes Yes Yes No Yes Yes Yes Yes No No 8
Effects of preventive
nutrition interventions
among adolescents on
health and nutritional
status in low- and mid-
dle-income countries


134
(Review)
Table 18. AMSTAR ratings for each systematic review: non-pregnant women of reproductive age (aged 19 to 49 years)
score
Library
Cochrane
(out of
a maxi-
mum of
11)
Supplementation
Better health.
Informed decisions.
Trusted evidence.
Abe 2016 Yes Yes Yes Yes Yes Yes Yes No Not ap- Yes Yes 9
plicable
Supplementation with
multiple micronutri-
ents for breastfeeding
women for improving
outcomes for the moth-
er and baby
Houston 2018 Yes Yes Yes Yes No Yes Yes No Yes Yes No 8
Efficacy of iron supple-

mentation on fatigue
and physical capacity in
non-anaemic iron-defi-
cient adults: a systemat-
ic review of randomised
controlled trials
Lassi 2020 Yes Yes Yes Yes Yes Yes Yes No Yes Yes No 9
Effects of preconception
care and periconception
interventions on mater-

nal nutritional status
and birth outcomes in
low- and middle-income
countries: a systematic
review
Low 2016 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
Daily iron supplemen-

tation for improving
anaemia, iron status and
135
(Review)
Table 18. AMSTAR ratings for each systematic review: non-pregnant women of reproductive age (aged 19 to 49 years) (Continued)
health in menstruating
women
Library
Cochrane
Sultan 2019 Yes Yes Yes Yes Yes Yes Yes No Yes Yes No 9
Oral versus intravenous

iron therapy for postpar-
tum anemia: a system-
atic review and meta-
Better health.
Informed decisions.
Trusted evidence.
analysis

Table 19. AMSTAR ratings for each systematic review: pregnant women (aged 15 to 49 years)
score
(out of
a maxi-

mum of
11)
Supplementation
Abu Hashim 2017 No Yes Yes Yes No Yes Yes Yes Yes Yes No 8
Lactoferrin or ferrous
salts for iron deficiency
anemia in pregnancy:
136
(Review)
Table 19. AMSTAR ratings for each systematic review: pregnant women (aged 15 to 49 years) (Continued)
a meta-analysis of ran-
domized trials
Library
Cochrane
Bhutta 2012 No Yes Yes Yes No No Yes No Yes No No 5
Is it time to replace iron

folate supplements in
pregnancy with multiple
micronutrients?
Better health.
Informed decisions.
Trusted evidence.
Buppasiri 2015 Yes Yes Yes Yes Yes Yes Yes No Yes Yes No 9
Calcium supplementa-
tion (other than for pre-
venting or treating hy-
pertension) for improv-
ing pregnancy and in-
fant outcomes
Daru 2016 Yes Yes Yes Yes No Yes Yes No Not ap- No No 6
plicable
Systematic review of
randomized trials of the
effect of iron supple-
mentation on iron stores
and oxygen carrying ca-
pacity in pregnancy
Das 2018 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
Lipid-based nutrient
supplements for mater-
nal, birth, and infant de-
velopmental outcomes

De-Regil 2015 Yes Yes Yes Yes Yes Yes Yes No Yes No Yes 9
Effects and safety of

periconceptional oral fo-
late supplementation for
preventing birth defects
Govindappagari 2019 Yes Yes Yes No No Yes Yes Cannot Yes No No 6

answer
Treatment of iron defi-
ciency anemia in preg-
137
(Review)
nancy with intravenous
versus oral iron: system-
Library
Cochrane
atic review and meta-
analysis
Haider 2013 Yes Yes No Cannot Yes Yes Yes No Yes Yes No 7
answer
Anaemia, prenatal iron
use, and risk of adverse
Better health.
Informed decisions.
Trusted evidence.
pregnancy outcomes:
meta-analysis
Haider 2011 Yes Cannot Yes Yes No Yes Yes Yes Yes Yes No 8
answer
Effect of multiple mi-
cronutrient supplemen-
tation during pregnan-
cy on maternal and birth
outcomes
Imdad 2012 No Yes Yes No Yes Yes Yes Not ap- Yes No No 6
plicable
Routine iron/folate sup-
plementation during
pregnancy: effect on ma-
ternal anaemia and birth
outcomes
Keats 2019 Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes 10
Multiple-micronutrient
supplementation for
women during pregnan-

cy
Lassi 2013 Yes Yes Yes Yes Yes Yes Yes No Yes Yes No 9
Folic acid supplementa-

tion during pregnancy
for maternal health and
pregnancy outcomes
McCauley 2015 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
138
(Review)
Vitamin A supplementa-
tion during pregnancy
Library
Cochrane
for maternal and new-
born outcomes
Peña-Rosas 2015b Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
Daily oral iron supple-

mentation during preg-
Better health.
Informed decisions.
Trusted evidence.
nancy
Peña-Rosas 2015a Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
Intermittent oral iron

supplementation during
pregnancy
Qassim 2018 No Yes Yes Yes Yes Yes Yes No No No No 6
Safety and efficacy of in-

travenous iron polymal-
tose, iron sucrose and
ferric carboxymaltose in
pregnancy: a systematic
review
Qassim 2019 Yes Yes Yes Yes No Yes Yes Yes Yes No No 8
Intravenous or oral iron

for treating iron defi-
ciency anaemia during
pregnancy: systematic
sis

Radhika 2019 No Yes Yes Yes No Yes Yes Yes Yes Yes No 8
Parenteral versus oral

iron for treatment of
iIron deficiency anaemia
during pregnancy and
post-partum: a system-
atic review
Reveiz 2011 Yes Yes Yes Yes Yes Yes Yes Yes Yes Not ap- Yes 10
plicable
139
(Review)
Treatments for iron-defi-
ciency anaemia in preg-
Library
Cochrane
nancy
Rumbold 2015 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
Vitamin C supplementa-
tion in pregnancy
Better health.
Informed decisions.
Trusted evidence.
Shi 2015 No Yes Yes Yes No Yes Yes Yes Yes Yes No 8
Intravenous iron sucrose

versus oral iron in the
treatment of pregnan-
cy with iron deficiency
anaemia: a systematic
review
Thorne-Lyman 2012 No No No No No Yes Yes No Yes No Yes 4
Vitamin A and
carotenoids during
pregnancy and mater-
nal, neonatal and in-
fant health outcomes: a
meta-analysis
Fortification
Suchdev 2015 Yes Yes Yes Yes Yes Yes Yes Yes Yes Not ap- No 9
plicable
Multiple micronutri-
ent powders for home

(point-of-use) fortifica-
tion of foods in pregnant
women

140
(Review)
Library
Cochrane
Table 20. AMSTAR ratings for each systematic review: mixed populations
Better health.
Informed decisions.
Trusted evidence.
score
(out of
a maxi-
mum of
11)
Supplementation
Arabi 2020 No Yes Yes No Yes Yes Yes Yes Yes Yes No 8
The effect of vitamin D

supplementation on he-
moglobin concentration:
meta-analysis
Basutkar 2019 Yes Yes Yes No No Yes Yes Yes Yes Yes Yes 9
Vitamin D supplementa-
tion in patients with iron
deficiency anaemia: a
systematic review and a
meta-analysis

Casgrain 2012 No Yes Yes No No Yes Yes No Yes No Yes 6
Effect of iron intake on

iron status: a systematic
sis of randomized con-
trolled trials
Gera 2009 Yes Cannot Yes Yes No Yes Yes No Yes Yes No 7
answer
141
(Review)
Table 20. AMSTAR ratings for each systematic review: mixed populations (Continued)
Effect of combining mul-
tiple micronutrients with
Library
Cochrane
iron supplementation on
Hb response in children:
systematic review of
randomized controlled
trials
Gera 2007a Yes No Cannot Yes No Yes Yes No Yes Yes No 6
Better health.
Informed decisions.
Trusted evidence.
answer
Effect of iron supple-
mentation on haemo-
globin response in chil-
dren: systematic re-
view of randomised con-
trolled trials
Silva Neto 2019 Yes Yes No Yes Yes Yes Yes No Yes No No 7
Effects of iron supple-

mentation versus di-
etary iron on the nutri-
tional iron status: sys-
tematic review with
als
Smelt 2018 No Cannot Yes Yes Yes Yes Yes No Yes No No 6

answer
The effect of vitamin B12
and folic acid supple-
mentation on routine
haematological parame-

ters in older people: an
individual participant
data meta-analysis
Tay 2015 No Yes Yes Yes Yes Yes Yes No Yes Yes Yes 9

meta-analysis: what is
the evidence for oral
iron supplementation in
142
(Review)
treating anaemia in el-
derly people?
Library
Cochrane
Tolkien 2015 No Yes Yes Yes Yes Yes Yes No Yes Yes No 8
Ferrous sulfate supple-

mentation causes sig-
nificant gastrointestinal
side-effects in adults: a
Better health.
Informed decisions.
Trusted evidence.
meta-analysis
Fortification
Das 2019b Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
Food fortification with

multiple micronutrients:
impact on health out-
comes in general popu-
lation
Field 2020 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
Wheat flour fortification

with iron for reducing
anaemia and improv-
ing iron status in popu-
lations
Finkelstein 2019 Yes Yes No Yes Yes Yes Yes No Yes No No 7
Iron biofortification in-

terventions to improve

iron status and function-
al outcomes
Garcia-Casal 2018 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
Fortification of maize
flour with iron for con-
trolling anaemia and
iron deficiency in popu-
lations
Gera 2012 Yes Yes Yes Yes No No Yes No Yes Yes No 7

143
(Review)
Effect of iron-fortified
foods on hematolog-
Library
Cochrane
ic and biological out-
comes: systematic re-
view of randomized con-
trolled trials
Hess 2016 Yes Yes Yes Yes No Yes Yes Yes Yes No No 8
Better health.
Informed decisions.
Trusted evidence.
Micronutrient fortified
condiments and noo-
dles to reduce anemia
in children and adults —
a Literature review and
meta-analysis
Huo 2015 No Yes Yes No No Yes Yes Yes Yes Cannot No 6

answer
Effect of NaFeEDTA-for-
tified soy sauce on ane-
mia prevalence in China:
als
Peña-Rosas 2019 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No 10
Fortification of rice with

vitamins and minerals
for addressing micronu-
trient malnutrition
Ramírez-Luzuriaga 2018 No Yes Yes No No Yes Yes No Yes Yes No 6

Impact of double-forti-
fied salt with iron and
iodine on hemoglo-
bin, anemia, and iron
deficiency anemia: a
meta-analysis
Sadighi 2019 No No Yes No No Yes Yes No Yes Yes No 5

144
(Review)
meta-analysis of the ef-
Library
Cochrane
fect of iron-fortified flour
on iron status of popula-
tions worldwide
Tablante 2019 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 11
Fortification of wheat
Better health.
Informed decisions.
Trusted evidence.
and maize flour with
folic acid for population
health outcomes
Yadav 2019 No Yes Yes Yes No Yes Yes No Yes Yes No 7
Meta-analysis of effica-
cy of iron and iodine for-
tified salt in improving
iron nutrition status
Geerligs 2003 No Cannot Yes Yes No Yes Yes Yes Not ap- Not ap- No 5
answer plicable plicable
Food prepared in iron
cooking pots as an inter-
vention for reducing iron
deficiency anaemia in
developing countries: a
systematic review

145

Informed decisions.
(Review)
Informed decisions.
Table 21. Results of included systematic reviews: infants (aged 6 to 23 months)

Review Comparison Outcome Number of Results GRADE as-
studies; num- sessment
ber of partici-
pants
Supplementation
Abdullah 2013 Iron supple- Post-treat- 2 trials; 68 Trial results not combined: Not assessed
mentation ment Hb level children
Efficacy of oral versus no (g/L) MD 11.5, 95% CI 5.1 to 17.9 (P < 0.01); 1 tri-
iron therapy in treatment or al, 28 children
improving the placebo
developmen- MD 2.7, 95% CI −1.7 to 7.1; 1 trial, 40 chil-
tal outcome of dren
pre-school chil-
dren with non-
anaemic iron
deficiency: a
systematic re-
view
Das 2019a LNS plus com- Anaemia (Hb < 5 trials: 2332 RR 0.79, 95% CI 0.69 to 0.90; significant re- Low
plementary 10 g/dL) children duction in anaemia for children receiving
Preventive feeding com- LNS plus complementary feeding com-
lipid-based nu- pared with no pared with no intervention
trient supple- intervention
ments given Adverse ef- 3 trials: 3382 RR 0.86, 95% CI 0.74 to 1.01; no evidence of Moderate
with comple- fects children a difference
mentary foods Defined as
to infants and deaths, hos-
young chil- pitalisations,
dren 6 to 23 congenital
months of age abnormali-
for health, nu- ties and life-
trition, and de- threatening
velopmental conditions re-
outcomes quiring an im-
mediate hos-
pital visit
LNS plus com- Anaemia (Hb < 2 trials: 557 RR 0.38, 95% CI 0.21 to 0.68; significant re- Low
plementary 10 g/dL) children duction in anaemia for children receiving
feeding com- LNS plus complementary feeding
pared with
MNP
Dekker 2010 Zinc supple- Hb (g/L) 21 trials; 3869 WMD 0.79, 95% CI −0.62 to 2.21; no evi- Not assessed
mentation children dence of a difference
Zinc supple- versus place-
mentation in bo or control
children is not
associated with
decreases in
hemoglobin
concentrations
(Review)
Informed decisions.
Table 21. Results of included systematic reviews: infants (aged 6 to 23 months) (Continued)
Pasricha 2013 Daily oral iron Hb (g/L) 26 trials; 5479 MD 7.22, 95% CI 4.87 to 9.57 (P < 0.001); sig- Not assessed
supplements children nificant increase in Hb concentration for
Effect of dai- versus control children receiving daily iron
ly iron supple-
mentation on Anaemia 17 trials; 4825 RR 0.61, 95% CI 0.50 to 0.74 (P < 0.001); sig- Not assessed
health in chil- children nificant reduction in anaemia for children
dren aged 4-23 receiving daily iron
months: a sys-
tematic re-
IDA 6 trials; 2145 RR 0.14, 95% CI 0.10 to 0.22 (P < 0.001); sig- Not assessed
view and meta-
children nificant reduction in IDA for children re-
analysis of ran-
ceiving daily iron
domised con-
trolled trials
ID 9 trials; 2464 RR 0.30, 95% CI 0.15 to 0.60 (P = 0.001); sig- Not assessed
children nificant reduction in ID for children receiv-
ing daily iron
Adverse ef- 3 trials; 912 RR 1.10, 95% CI 0.98 to 1.25; no evidence of Not assessed
fect: 'any side children a difference
effect'
Adverse ef- 3 trials; 1020 RR 1.38, 95% CI 1.10 to 1.73 (P = 0.006); sig- Not assessed
fect: 'vomit- children nificant increase in vomiting for children
ing' receiving daily iron
fect: 'diar- children a difference
rhoea (preva-
lence)'
Adverse ef- 5 trials; num- RR 0.98, 95% CI 0.88 to 1.09; no evidence of Not assessed
fect: 'diar- ber of partici- a difference
rhoea (inci- pants: not re-
dence)' ported
fect: 'consti- children a difference
pation'
Petry 2016b Children 6 Hb (g/L) 30 trials; 6569 MD 4.10,95% CI 2.80 to 5.30 (P < 0.001); sig- Moderate
months to 23 children nificant increase in Hb concentration for
The effect of months: dai- children receiving daily iron intervention
low dose iron ly iron admin-
and zinc intake istration (≤ 15 Anaemia 22 trials; 5647 RR 0.59, 95% CI 0.49 to 0.70 (P < 0.001); sig- Low
on child mi- mg/day) ver- children nificant decrease in anaemia for children
cronutrient sta- sus control receiving daily iron intervention
tus and devel-
opment during
IDA 8 trials; 3464 RR 0.20, 95% CI 0.11 to 0.37 (P < 0.001); sig- High
the first 1000
children nificant decrease in IDA for children receiv-
days of life: a
ing daily iron intervention
systematic re-
view and meta-
analysis ID 13 trials; 3698 RR 0.22, 95% CI 0.14 to 0.35 (P < 0.001); sig- High
children nificant decrease in ID for children receiv-
ing daily iron intervention
Diarrhoea 8 trials; num- No beneficial effect of iron on diarrhoea Not assessed

ber of partici-
pants: not re-
ported
(Review)
Informed decisions.
Pratt 2015 Iron supple- Hb (g/L) 1 trial; 391 A statistically significant difference in Not assessed
mentation children mean Hb levels for children receiving dai-
A review of the versus control ly 12.5 mg iron (P = 0.046), but not for the
strategies used group receiving weekly supplements
to reduce the
prevalence of Anaemia 2 trials; 675 Trial 1: at 9 months, 21% of infants were Not assessed
iron deficiency prevalence children anaemic, but no differences between
and iron defi- groups for occurrence of anaemia
ciency anaemia
in infants aged Trial 2: dose–response effect in the group
6-36 months given daily, but not weekly supplements
ID 1 trial; 284 At 9 months, 81% of infants had ID, but no Not assessed
children differences between groups for occurrence
of ID
Iron-fortified Hb (g/L) 1 trial; 115 Hb was positively associated with treat- Not assessed
milk versus children ment (P < 0.001)
control
Anaemia 2 trials; 910 Trial 1: decline from 41.4% to 12.1% in in- Not assessed
prevalence children tervention group and no decline in control
group
Trial 2: decline in intervention group from

44.5% to 12.7% to 4.0%, and in control
group from 42.6% to 19.7% to 9.4%, from
baseline, to 6 and to 12 months
Micronutrient Hb (g/L) 2 trials; 3633 Trial 1: + 6.1 g/L in intervention group com- Not assessed
sprinkles ver- children pared with + 2.2 g/L in control group, from
sus control baseline to 12 and to 18 months, P < 0.001
Trial 2: + 7 g/L in intervention group com-

pared with + 2 g/L in control group, from
baseline to 2 months, P < 0.001
Anaemia 2 trials; 3633 Trial 1: reduction of 20.6% in the inter- Not assessed
prevalence children vention group (reduction of moderate
anaemia by 27.1%), from baseline to 6
months, P < 0.001
Trial 2: reduction from 72% to 52% in the

intervention group, increase from 72% to
75% in the control group, from baseline to
2 months, P < 0.001
Food-based Hb (g/L) 1 trial; 225 No evidence of intervention effects on Not assessed

strategies: children haemoglobin
red meat, for-

tified cow's
milk versus
control
Efficacy of dif- Hb (g/L) 1 trial; 2666 All treatments: significant increase in Hb Not assessed
ferent strate- children
gies:
Anaemia 1 trial; 2666 Anaemia prevalence significantly more re- Not assessed
iron supple- prevalence children duced in multiple micronutrient supple-
ment, iron ment (72%) and iron and folic acid sup-
(Review)
Informed decisions.
and folic acid plementation (69%) groups than fortified
supplement, complementary food (45%) group
multiple mi-
cronutrient
supplements,
fortified com-
plementary
food or forti-
fied water
Fortification
Dewey 2009 Home fortifi- Hb (g/L) 3 trials; 1263 MD −0.91, 95% CI −11.96 to 10.14; no evi- Not assessed
cation treat- children dence of a difference
Systematic re- ment versus
view and meta- iron drops Anaemia 3 trials; 1263 RR 1.04, 95% CI 0.76 to 1.41; no evidence of Not assessed
analysis of (treatment) children a difference
home fortifica-
tion of comple-
Diarrhoea 2 trials; 808 SMD −0.34, 95% CI −0.71 to 0.03; no evi- Not assessed
mentary foods
children dence of a difference
Home fortifi- Hb (g/L) 8 trials; 2649 MD 5.06, 95% CI 2.29 to 7.83; significant in- Not assessed
cation versus children crease in Hb concentration for children re-
no interven- ceiving home fortification
tion or place-
bo (preven- Anaemia 8 trials; 4331 RR 0.54, 95% CI 0.46 to 0.64; significant re- Not assessed
tion) children duction in anaemia for children receiving
home fortification
ID 3 trials; 1210 RR 0.44, 95% CI 0.22 to 0.86; significant re- Not assessed
children duction in ID for children receiving home
fortification
Diarrhoea 5 trials; 1195 RR 1.07, 95% CI 0.78 to 1.47; no evidence of Not assessed
children a difference
Eichler 2012 Iron fortifica- Hb (g/L) 13 trials; 2274 MD 6.20, 95% CI 3.40 to 8.90; significant in- Not assessed
tion of milk children crease in Hb concentration for children re-
Effects of mi- and cereals ceiving iron-fortified milk and cereals
cronutrient versus non-
fortified milk fortified food Anaemia 11 trials; 3100 RR 0.50, 95% CI 0.33 to 0.75; significant re- Not assessed
and cereal food children duction in anaemia for children receiving
for infants and iron-fortified milk and cereals
children: a sys-
tematic review
Matsuyama Fortified milk Hb (g/L) 9 trials; num- MD 5.89, 95% CI −0.24 to 12.02; no evi- Not assessed
2017 versus control ber of partici- dence of a difference
milk pants: not re-
Effect of for- ported
tified milk on
growth and nu- Anaemia 9 trials; num- OR 0.32, 95% CI 0.15 to 0.66 (P = 0.000); sig- Not assessed
tritional status ber of partici- nificant reduction in anaemia for children
in young chil- pants: not re- receiving fortified milk
dren: a system- ported
atic review and
meta-analysis
(Review)
Informed decisions.
Salam 2013 MNP versus Hb (g/L) 14 trials; 9132 SMD 0.98, 95% 0.55 to 1.40 (P < 0.001); sig- Moderate
control or no children nificant improvement in Hb for children re-
Effectiveness of intervention ceiving MNP
micronutrient
powders (MNP) Anaemia 11 trials; 2524 RR 0.66, 95% CI 0.57 to 0.77 (P < 0.001); sig- Moderate
in women and children nificant reduction in anaemia for children
children receiving MNP
IDA 7 trials; 1390 RR 0.43, 95% CI 0.35 to 0.52, significant re- Moderate
children duction in IDA for children receiving MNP
Diarrhoea 4 trials; 3371 RR 1.04, 95% CI 1.01 to 1.06 (P = 0.002); sig- Moderate
children nificant increase in diarrhoea for children
receiving MNP
Recurrent di- 1 trial; num- RR 2.86, 95% Cl 0.12 to 69.0; no evidence of Moderate
arrhoea ber of partici- a difference
pants: not re-
ported
Suchdev 2020 Home (point- Hb (g/L) 20 trials; MD 2.74, 95% CI 1.95 to 3.53 (P < 0.001); sig- Low
of-use) for- 1,050,947 chil- nificant increase in Hb concentration for
Home fortifica- tification of dren children receiving MNP
tion of foods foods with
with multiple MNP versus Anaemia 16 trials; 9927 RR 0.82, 95% CI 0.76 to 0.90 (P < 0.001); sig- Moderate
micronutrient no interven- children nificant reduction in anaemia for children
powders for tion or place- receiving MNP
health and nu- bo
trition in chil-
ID 7 trials; 1634 RR 0.47, 95% CI 0.39 to 0.567 (P < 0.001); High
dren under two
children significant reduction in ID for children re-
years of age
ceiving MNP
Diarrhoea 5 trial; 5579 OR 1.05, 95% CI 0.82 to 1.35; no evidence of Not assessed
children a difference
Home (point- Hb (g/L) 2 trials; 278 MD −2.81, 95% CI −10.84 to 5.22; no evi- Very low
of-use) for- children dence of a difference
tification of
foods with Anaemia 1 trial; 145 RR 0.89, 95% CI 0.58 to 1.39; no evidence of Low
MNP versus an children a difference
iron-only sup-
plement Diarrhoea 1 trial; 262 RR 0.52, 95% CI 0.38 to 0.72 (P < 0.001); sig- Not assessed
children nificant reduction in diarrhoea for children
receiving MNP
Vomiting 1 trial; 262 RR 0.58, 95% CI 0.35 to 0.95 (P = 0.029); sig- Not assessed
children nificant reduction in vomiting for children
receiving MNP
Staining of 2 trials; 395 RR 0.37, 95% CI 0.16 to 0.82 (P = 0.02); sig- Not assessed
teeth children nificant reduction in teeth staining for chil-
dren receiving MNP
Stool dis- 2 trials; 395 RR 0.80, 95% CI 0.66 to 0.98 (P = 0.04); sig- Not assessed
colouration children nificant reduction in stool discolouration
for children receiving MNP
(Review)
Informed decisions.
Kristjansson Supplemen- Change in Hb 5 trials; 300 SMD 0.49, 95% CI 0.07 to 0.91 (P = 0.002); Not assessed
2015 tary feeding (g/L) children significant increase in Hb concentration for
versus control children receiving supplementary feeding
Food supple-
mentation for
improving the
physical and
psychosocial
health of so-
cio-econom-
ically disad-
vantaged chil-
dren aged three
months to five
years
Shapiro 2019 Caterpillar ce- Hb (g/dL) 1 trial; 175 Mean (SD) caterpillar cereal: 10.7 (1.6), usu- Not assessed
real versus children al diet: 10.1 (1.8) (P < 0.05)
A systematic usual diet
review investi- IDA preva- 1 trial; 175 Caterpillar cereal: 26%, usual diet control: Not assessed
gating the rela- lence children 50% (P < 0.01)
tion between
animal-source
Beef versus Hb (g/dL) 1 trial; 1602 No significant difference in Hb levels be- Not assessed
food consump-
fortified rice- children tween intervention and control group
tion and stunt-
soy cereal
ing in chil-
dren aged 6-60
months in low Food forti- Hb (g/dL) 1 trial; 190 No significant difference in Hb levels be- Not assessed
and middle-in- fied with fish children tween intervention and control group
come countries powder versus
food with or
without vita-
mins and min-
erals
CI: confidence interval; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; LNS: lipid-based nutrient supplements; MD:
mean difference; MNP: micronutrient powders; OR: odds ratio; RR: risk ratio; SMD: standard mean difference; WMD: weighted mean
difference.
Table 22. Results of included systematic reviews: preschool and school-aged children (aged 2 to 10 years)
ber of partici-
pants
Supplementation
Low 2013 Iron supple- Hb (g/L) 28 trials; 6545 MD 8.38, 95% CI 6.21 to 10.56 (P < 0.001), Not assessed
mentation children significant increase in Hb concentration for
Effects of dai- versus place- children receiving iron supplementation
ly iron sup- bo or control
plementa- Anaemia 7 trials; 1763 RR 0.50, 95% CI 0.39 to 0.64 (P < 0.001), sig- Not assessed
tion in pri- children nificant reduction in anaemia for children
mary-school- receiving iron supplementation
aged children:
systematic
review and
meta-analysis
(Review)
Informed decisions.
Table 22. Results of included systematic reviews: preschool and school-aged children (aged 2 to 10 years) (Continued)
of randomized
IDA 2 trials; 334 RR 0.12, 95% CI 0.02 to 0.66 (P = 0.01), signif- Not assessed
controlled tri-
children icant reduction in IDA for children receiving
als
iron supplementation
ID 4 trials; 1020 RR 0.21, 95% CI 0.07 to 0.63 (P = 0.006), sig- Not assessed
children nificant reduction in IDA for children receiv-
ing iron supplementation
Adverse 4 trials; 576 RR 1.30, 95% CI 0.89 to 1.91, no evidence of a Not assessed
event: 'gas- children difference
trointestinal
upset'
Adverse 2 trials; 202 RR 3.44, 95% CI 0.66 to 19.68, no evidence of Not assessed
event: 'consti- children a difference
pation'
Adverse 2 trials; 202 RR 0.86, 95% CI 0.13 to 5.67, no evidence of a Not assessed
event: 'vomit- children difference
ing'
De-Regil 2011 Intermittent Hb (g/L) 19 trials; 3032 MD 5.20, 95 % CI 2.51 to 7.88 (P < 0.001), sig- Low
supplementa- children nificant increase in Hb concentration for
Intermittent tion with iron children receiving intermittent iron supple-
iron supple- alone or with mentation versus placebo or no intervention
mentation for other nutri-
improving nu- ents versus Anaemia 10 trials; 1824 RR 0.51, 95 % CI 0.37 to 0.72 (P < 0.001), sig- Moderate
trition and de- placebo or no children nificant reduction in anaemia for children
velopment in intervention receiving intermittent iron supplementation
children un- versus placebo or no intervention
der 12 years of
age
ID 3 trials; 431 RR 0.24, 95 % CI 0.06 to 0.91 (P = 0.036), sig- Very low
children nificant reduction in ID for children receiv-
ing intermittent iron supplementation ver-
sus placebo or no intervention
Any side ef- 1 trial; 53 chil- RR 3.87, 95% CI 0.19 to 76.92, no evidence of Not assessed
fects dren a difference
Intermittent Hb (g/L) 19 trials; 2851 MD −0.60, 95% CI −1.54 to 0.35, no evidence Low
iron supple- children of a difference
mentation
versus daily Anaemia 6 trials; 980 RR 1.23, 95% CI 1.04 to 1.47 (P = 0.017), sig- Low
iron supple- children nificant reduction in anaemia for children
mentation receiving intermittent iron supplementation
versus daily iron
ID 1 trial; 76 chil- RR 4.00, 95% CI 1.23 to 13.05, (P = 0.022), sig- Very low
dren nificant increase in ID for children receiving
intermittent iron supplementation versus
daily iron
Diarrhoea 2 trials; 122 RR 1.17, 95% CI 0.60 to 2.28, no evidence of a Not assessed
children difference
Any side ef- 4 trials; 895 RR 0.60, 95% CI 0.19 to 1.87, no evidence of a Not assessed
fects children difference
(Review)
Informed decisions.
Mayo-Wilson Zinc versus no Blood Hb con- 26 trials; 6024 SMD 0.05, 95% CI -0.00 to 0.10, no evidence Not assessed
2014a zinc centration children of a difference
Zinc supple- Prevalence of 13 trials; 4287 RR 1.00, 95% CI 0.95 to 1.06, no evidence of a Not assessed
mentation anaemia children difference
for prevent-
ing mortali-
Prevalence of 10 trials; 3149 RR 0.99, 95% CI 0.89 to 1.10, no evidence of a Not assessed
ty, morbidity,
ID children difference
and growth
failure in chil-
dren aged 6 Side effect: 3 trials; 850 RR 1.13, 95% CI 1.00 to 1.27, no evidence of a Not assessed
months to 12 'participants children difference
years of age with ≥ 1 side
effect'
Side effect: 5 trials; 4095 RR 1.68, 95% CI 1.61 to 1.75 (P < 0.001), sig- Not assessed
'vomiting children nificant increase in vomiting episodes for
episodes' children receiving zinc supplementation
Side effect: 5 trials; 35192 RR 1.29, 95% CI 1.14 to 1.46 (P < 0.001), sig- High
'participants children nificant increase in ≥ 1 vomiting episode for
with ≥ 1 vom- children receiving zinc supplementation
iting episode'
Zinc versus Blood Hb con- 8 trials; 1341 SMD −0.23, 95% CI −0.34 to −0.12 (P < 0.001), Not assessed
zinc plus iron centration children difference favouring zinc plus iron
Prevalence of 3 trials; 482 RR 0.78, 95% CI 0.67 to 0.92 (P = 0.003), sig- Not assessed
anaemia children nificant reduction anaemia prevalence for
children receiving zinc plus iron
Prevalence of 2 trials; 248 RR 0.12, 95% CI 0.04 to 0.32 (P < 0.001), re- Not assessed
ID children duction in ID prevalence for children receiv-
ing zinc plus iron
Thompson Iron supple- Hb (g/L) 9 trials; 1690 MD 6.97, 95% CI 4.21 to 9.72, significant in- High
2013 mentation children crease in Hb concentration for children re-
versus control ceiving iron supplementation
Effects of dai-
ly iron supple- Anaemia 1 trial; 359 144/183 (79%) anaemic in iron group, Very low
mentation in children 142/176 (81%) anaemic in control group; no
2- to 5-year- evidence of a difference
old children:
systematic
review and
meta-analysis
Fortification
Aaron 2015 Non-dairy Hb (g/L) 8 trials; 3835 MD 2.76, 95% CI 1.19 to 4.33 (P = 0.004), sig- Moderate
MMN-fortified children nificant increase in Hb concentration for
Multiple-mi- beverages ver- children receiving MMN-fortified beverages
cronutrient sus control
fortified non- Anaemia 6 trials; 2828 RR 0.63, 95% CI 0.54 to 0.73 (P < 0.001), sig- Moderate
dairy bever- children nificant reduction in anaemia for children
age interven- receiving MMN-fortified beverages
tions reduce
the risk of
anemia and
iron deficien-
(Review)
Informed decisions.
cy in school-
ID 7 trials; 2523 RR 0.32, 95% CI 0.23 to 0.45 (P < 0.001), sig- Moderate
aged children
children nificant reduction in ID for children receiving
in low-mid-
MMN-fortified beverages
dle income
countries: a
systematic IDA 3 trials; 1649 RR 0.13, 95% CI 0.07 to 0.25 (P < 0.001), sig- Low
review and children nificant reduction in IDA for children receiv-
meta-analysis ing MMN-fortified beverages
Das 2013a Zinc fortifica- Serum Hb 1 trial; 19 chil- SMD 0.28, 95% CI −0.62 to 1.19, no evidence Not assessed
tion versus dren of a difference
Systematic re- control (with
view of zinc a regular diet
fortification or unfortified
trials foods)
De-Regil 2017 Point-of-use Hb (g/L) 11 trials; 2746 MD 3.37, 95% CI 0.94 to 5.80 (P = 0.007), sig- Low
fortification children nificant decrease in Hb concentration for
Point-of-use of foods with children receiving MNP
fortification MNP versus
of foods with no interven- Anaemia 10 trials; 2448 RR 0.66, 95% CI 0.49 to 0.88 (P = 0.005), sig- Moderate
micronutrient tion or place- children nificant decrease in anaemia for children re-
powders con- bo ceiving MNP
taining iron
in children of
IDA 3 trials; 918 RR 0.28, 95% CI 0.07 to 1.10, no evidence of a Not assessed
preschool and
children difference
school age
ID 5 trials; 1364 RR 0.35, 95% CI 0.27 to 0.47, significant de- Moderate
children crease in iron deficiency for children receiv-
ing MNP
Adverse ef- 1 trial; 90 chil- RR 1.09, 95% CI 0.16 to 7.42. no evidence of a Moderate
fects dren difference
Diarrhoea 2 trials; 366 RR 0.97, 95% CI 0.53 to 1.78, no evidence of a Low

children difference
Eichler 2019 Fortified dairy Hb g/L 14 trials; 4855 MD 0.90, 95% CI −0.10 to 1.80, no evidence of Very low
products and children and a difference
Health effects cereal food adolescents
of micronutri- versus no for-
ent fortified tification with Anaemia 12 trials; 1149 RR 0.87, 95% CI 0.76 to 1.01, no evidence of a Very low
dairy prod- MN children difference
ucts and ce-
real food for
IDA 5 trials; 148 RR 0.38, 95% CI 0.18 to 0.81, significant re- Very low
children and
children duction in IDA for children receiving fortifi-
adolescents: a
cation
systematic re-
view
ID 8 trials; 519 RR 0.62, 95% CI 0.40 to 0.97, significant re- Very low
children duction in ID for children receiving fortifica-
tion
Adverse 3 trials Three studies reported that no significant Low

events adverse events were related to the study
food or to the fortification
(Review)
Informed decisions.
CI: confidence interval; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; MD: mean difference; MMN: multiple-
micronutrient; MN: micronutrient; MNP: micronutrient powders; OR: odds ratio; RR: risk ratio; SMD: standardised mean difference.
Table 23. Results of included systematic reviews: adolescent children (aged 11 to 18 years)
ber of partici-
pants
Supplementation
Fernán- Intermittent Hb (g/L) 15 trials; 2886 MD 5.19, 95% CI 3.07 to 7.32 (P < 0.001), sig- Moderate
dez-Gaxiola iron supple- women nificant increase in Hb levels for women re-
2019 mentation ceiving intermittent iron supplementation
(alone or with
Intermittent any other mi- Anaemia 11 trials; 3135 RR 0.65, 95% CI 0.49 to 0.87 (P = 0.0038), sig- Low
iron supple- cronutrients) women nificant reduction in anaemia for women re-
mentation versus no sup- ceiving intermittent iron supplementation
for reducing plementation
anaemia and or placebo IDA 1 trial; 97 RR 0.07, 95% CI 0.00 to 1.16, no evidence of a Low
its associated
women difference
impairments
in adoles-
cent and adult ID 3 trials; 624 RR 0.50, 95% CI 0.24 to 1.04, no evidence of a Low
menstruating women difference
women
Any adverse 3 trials; 630 RR 1.98, 95% CI 0.31 to 12.72, no evidence of Moderate
side effect women a difference
Intermittent Hb (g/L) 10 trials; 2127 MD 0.43, 95% CI −1.44 to 2.31, no evidence of Low
iron supple- women a difference
mentation
versus daily Anaemia 8 trials; 1749 RR 1.09, 95% CI 0.93 to 1.29, no evidence of a Moderate
iron supple- women difference
mentation
ID 1 trial; 198 RR 4.30, 95% CI 0.56 to 33.20, no evidence of Very low
women a difference
Any adverse 6 trials; 1166 RR 0.41, 95% CI 0.21 to 0.82 (P = 0.011), sig- Low
side effect women nificant reduction in any adverse side effects
for women receiving intermittent iron sup-
plementation versus iron supplementation
Neuberger Iron versus Hb (g/L) 16 trials, 5261 MD 7.50, 95% CI 4.80 to 10.10, significant Not assessed
2016 placebo/no children increase in Hb concentration at the end of
treatment treatment for children receiving iron supple-
Oral iron sup- 7 trials, 2481 mentation
plements for anaemic chil-
children in dren at base- MD 9.50, 95% CI 3.80 to 15.10, significant
malaria-en- line increase in Hb concentration at the end of
demic areas treatment for anaemic children receiving
9 trials, 2780 iron supplementation
non anaemic
children at MD 6.10, 95% CI 3.80 to 8.50, significant in-
baseline crease in Hb concentration at the end of
treatment for non anaemic children receiv-
12 trials, 2462 ing iron supplementation
children
(Review)
Informed decisions.
Table 23. Results of included systematic reviews: adolescent children (aged 11 to 18 years) (Continued)
MD 6.70, 95% CI 4.20 to 9.20 (P<0.001), sig-
nificant improvement in haemoglobin from
the baseline at end of treatment
Anaemia (as 15 trials, 3784 RR 0.63, 95% CI 0.49 to 0.82, significant re- Not assessed
defined in the children duction in anaemia for children receiving
trial) iron supplementation
Iron plus folic Hb (g/L) 1 trial, 124 MD 9.00, 95% CI 5.10 to 12.90, significant Not assessed
acid versus children increase in Hb concentration at the end of
placebo treatment for children receiving iron plus
folic acid supplementation
defined in the children duction in anaemia for children receiving
trial) iron plus folic acid supplementation
Iron plus anti- Hb (g/L) 1 trial, 151 MD 9.10, 95% CI 4.70 to 13.50, significant Not assessed
malarial ver- children increase in Hb concentration at the end of
sus placebo treatment for children receiving iron plus
antimalarial supplementation
defined in the children duction in anaemia at the end of treatment
trial) for children receiving iron plus antimalarial
1 trial, 420 supplementation
children
RR 0.37, 95% CI 0.26 to 0.54, significant re-
duction in anaemia at the end of follow-up
for children receiving iron plus antimalarial
supplementation
Salam 2016 Iron or iron Hb (g/L) Not reported MD 1.94, 95% CI 1.48 to 2.41, significant in- Not assessed
folic acid sup- crease in Hb concentration for adolescents
Interventions plementation receiving supplementation
to improve alone or in
adolescent combination Anaemia 11 trials; RR 0.69, 95% CI 0.62 to 0.76, significant re- Moderate
nutrition: a with other mi- 11,861 adoles- duction in anaemia for adolescents receiv-
systematic cronutrient cents ing supplementation
review and supplemen-
meta-analysis tation versus
control
Nutritional IDA 1 trial; 14 RR 0.34, 95% CI 0.13 to 0.89, significant re- Low
supplementa- pregnant ado- duction in IDA for pregnant adolescents re-
tion and coun- lescents ceiving nutritional supplementation and
selling versus counselling
control
Salam 2020 Daily iron sup- Anaemia 1 trial, 1160 RR 1.04, 95% CI 0.88 to 1.24, no significant Low
plementation participants reduction in anaemia for participants receiv-
Effects of pre- with or with- ing daily iron supplementation with or with-
ventive nutri- out folic acid out folic acid versus placebo/no supplemen-
tion interven- versus place- tation/no fortification
tions among bo/no supple-
adolescents mentation/no
on health and fortification
nutrition-
al status in Weekly iron Anaemia 1 trial, 1274 RR 1.07, 95% CI 0.91 to 1.26, no significant Low
low- and mid- supplemen- participants reduction in anaemia for participants receiv-
(Review)
Informed decisions.
Table 23. Results of included systematic reviews: adolescent children (aged 11 to 18 years) (Continued)
dle-income tation with or ing weekly iron supplementation with or
countries without folic without folic acid versus placebo/no supple-
acid versus mentation/no fortification
placebo/no
supplementa-
tion/no fortifi-
cation
Iron supple- Hb (g/L) 4 trials, 1020 MD 0.42 g/L, 95% CI 0.13 to 0.71, significant Low
mentation participants increase in Hb concentration for partici-
with or with- pants receiving iron supplementation with
out folic acid or without folic acid compared to no supple-
versus no sup- mentation
plementation
Fortification
Salam 2020 MMN fortifica- Hb (g/L) 2 trials, 1102 MD −0.10 g/L, 95% CI -0.88 to 0.68, no signifi- Low
tion versus no participants cant increase in Hb concentration for partic-
Effects of pre- fortification ipants receiving MMN fortification compared
ventive nutri- to no fortification
tion interven-
tions among
adolescents
on health and
nutrition-
al status in
low- and mid-
dle-income
countries
CI: confidence interval; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; MD: mean difference; MMN: multiple
micronutrient; RR: risk ratio.
Table 24. Results of included systematic reviews: non-pregnant women of reproductive age (aged 19 to 49 years)
ber of partici-
pants
Supplementation
Abe 2016 No data No data No data No data No data
Supplementa-
tion with multi-
ple micronutri-
ents for breast-
feeding women
for improving
outcomes for
the mother and
baby
Houston 2018 Iron therapy Hb (g/L) 12 trials; 298 MD 4.01, 95% CI 1.22 to 6.81 (P = 0.005) Not assessed
(oral, IV, IM) participants
Efficacy of iron versus control
supplemen-
(Review)
Informed decisions.
Table 24. Results of included systematic reviews: non-pregnant women of reproductive age (aged 19 to 49
tation on
years) fa-
(Continued)
Anaemia 2 trials; 327 Anaemia was less common in patients ran- Not assessed
tigue and phys-
participants domised to receive iron supplementation
ical capacity in
non-anaemic
iron-deficient Gastrointesti- 3 trials; 262 Significantly increased in 1 trial using IM Not assessed
adults: a sys- nal intoler- participants iron administration but not in the 2 trials
tematic review ance that used oral administration
of randomised
controlled trials Nausea 4 trials; 540 2 trials using IV administration of iron re- Not assessed
participants ported significantly increased nausea,
whereas nausea was not increased in pa-
tients who received iron by oral adminis-
tration
Constipation 1 trial; 24 par- 1 participant in the intervention group suf- Not assessed
ticipants fered by constipation compared with 0 in
the control group
Diarrhoea 2 trials; 114 2 participants in the intervention group Not assessed

participants suffered from diarrhoea compared with 3
in the control group
Lassi 2020 Iron folic acid Anaemia 6 trials; 3430 RR 0.66, 95% CI 0.53 to 0.81, significant re- Very low
supplemen- women duction in anaemia for women receiving
Effects of pre- tation versus iron folic acid supplementation
conception placebo
care and peri- Anaemia - 6 trials; 2661 RR 0.70, 95% CI 0.55 to 0.88, significant re- Very low
conception in- weekly sup- women duction in anaemia for women receiving
terventions on plementation weekly iron folic acid supplementation
maternal nu-
tritional status
Anaemia - dai- 2 trials; 1532 RR 0.49, 95% CI 0.21 to 1.12, significant re- Very low
and birth out-
ly supplemen- women duction in anaemia for women receiving
comes in low-
tation daily iron folic acid supplementation
and middle-in-
come coun-
tries: a system-
atic review
Low 2016 Daily oral iron Hb at the end 51 trials; 6861 MD 5.30, 95% CI 4.14 to 6.45 (P < 0.001), sig- High
supplementa- of therapy (g/ women nificant increase in Hb concentration for
Daily iron sup- tion versus no L) women receiving daily oral iron
plementation daily oral iron
for improv- supplementa- Anaemia at 10 trials; 3273 RR 0.39, 95% CI 0.25 to 0.60 (P = 0.000017), Moderate
ing anaemia, tion the end of women significant reduction in anaemia for
iron status therapy women receiving daily oral iron
and health in
menstruating
IDA at the end 1 trial; 55 Not estimated Not assessed
women
of therapy women
ID at the end 7 trials; 1088 RR 0.62, 95% CI 0.50 to 0.76 (P < 0.001), sig- Moderate
of therapy women nificant reduction in ID for women receiv-
ing daily oral iron
Any adverse 7 trials; 901 RR 2.14, 95% CI 0.94 to 4.86, no evidence of Low
side effect (to- women a difference
tal)
(Review)
Informed decisions.
Table 24. Results of included systematic reviews: non-pregnant women of reproductive age (aged 19 to 49
years) (Continued)
Sultan 2019 IV iron versus Hb (g/L) 1 11 trials (1236 MD 10.00, 95% CI 5.00 to 15.00 (P < 0.0001), Not assessed
oral iron week postpar- women) significant increase in Hb levels for women
Oral versus tum receiving IV iron
intravenous
iron therapy Hb (g/L) 2 7 trials (980 MD 12.00, 95% CI 5.00 to 19.00 (P = 0.0007), Not assessed
for postpar- weeks post- women) significant increase in Hb levels for women
tum anemia: a partum receiving IV iron
systematic re-
view and meta-
Hb (g/L) 3 2 trials (346 MD 13.00, 95% CI 0.60 to 26.00 (P = 0.04), Not assessed
analysis
weeks post- women) significant increase in Hb levels for women
partum receiving IV iron
Hb (g/L) 4 4 trials (583 MD 7.00, 95% CI −3.00 to 16.00 (P = 0.18), Not assessed
weeks post- women) no evidence of a difference
partum
Hb (g/L) 6 4 trials (385 MD 9.00,95% CI 4.00 to 13.00 (P = 0.0003), Not assessed

weeks post- women) significant increase in Hb levels for women
partum receiving IV iron
Treatment-re- 4 trials (281 OR 6.95, 95% CI 1.56 to 31.03 (P = 0.01), Not assessed
lated side ef- women) women receiving IV iron had increased skin
fects: skin flushing
flushing
Treatment-re- 8 trials (1535 OR 0.08, 95% CI 0.03 to 0.21 (P < 0.00001), Not assessed
lated side ef- women) women receiving IV iron had decreased
fects: consti- constipation
pation
Treatment-re- 3 trials (304 OR 0.07, 95% CI 0.01 to 0.42 (P = 0.004), Not assessed
lated side ef- women) women receiving IV iron had decreased
fects: dyspep- dyspepsia
sia
Other treat- 1 to 6 trials No difference between IV iron and oral iron Not assessed
ment-related for nausea, muscle cramps, alanine trans-
side effects ferase rise, aspartate transaminase rise,
headache, anaphylaxis, urticaria, rash, in-
fection
CI: confidence interval; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; IM: intramuscular; IV: intravenous; MD: mean
difference; RCTs: randomised controlled trials; RR: risk ratio.
Table 25. Results of included systematic reviews: pregnant women (aged 15 to 49 years)
ber of partici-
pants
Supplementation
https:// Oral bovine Hb levels at 4 4 trials; 600 MD 7.70, 95% CI 0.40 to 15.50 (P = 0.04), sig- Low
revman.cochrane.org/
lactoferrin weeks (g/L) women nificant increase in Hb level for women re-
#/498917022710493686/
versus oral ceiving oral bovine lactoferrin
dash-
(Review)
Informed decisions.
Table 25. Results of included systematic reviews: pregnant women (aged 15 to 49 years) (Continued)
board/htm- ferrous iron
Gastrointesti- 2 trials; 328 OR 0.11, 95% CI 0.05 to 0.22 (P < 0.001), sig- Moderate
lView/2.175.57?re- preparations
nal side ef- women nificant reduction in epigastric discomfort
vertEn-
fects: 'epigas- for women receiving oral bovine lactoferrin
abled=false#REF-Abu-
tric discom-
Hashim-2017
fort'
Lactoferrin or
ferrous salts for Gastrointesti- 2 trials; 328 OR 0.32, 95% CI 0.15 to 0.67 (P = 0.002), sig- Moderate
iron deficiency nal side ef- women nificant reduction in vomiting for women
anemia in preg- fects: 'vomit- receiving oral bovine lactoferrin
nancy: a meta- ing'
analysis of ran-
domized trials Gastrointesti- 2 trials; 328 OR 0.22, 95% CI 0.12 to 0.40 (P < 0.001), Moderate
nal side ef- women significant reduction in constipation for
fects: 'consti- women receiving oral bovine lactoferrin
pation'
Gastrointesti- 1 trial; 228 OR 0.21, 95% CI 0.12 to 0.39 (P < 0.001), Moderate
nal side ef- women significant reduction in abdominal col-
fects: 'abdom- icky pain for women receiving oral bovine
inal colicky lactoferrin
pain'
Gastrointesti- 1 trial; 228 OR 0.01, 95% CI 0.00 to 0.22 (P = 0.002), sig- Moderate
nal side ef- women nificant reduction in dark stool for women
fects: 'dark receiving oral bovine lactoferrin
stool'
Gastrointesti- 1 trial; 228 OR 0.00, 95% CI 0.00 to 0.00, no evidence of Not assessed
nal side ef- women a difference
fects: 'diar-
rhoea'
https:// MMN versus Maternal Hb 4 trials; num- SMD −0.01, 95% CI −0.08 to 0.06, no evi- Low
iron folate (g/L) ber of partici- dence of a difference
#/498917022710493686/ pants: not re-
dash- ported
board/htm-
lView/2.175.57?re- Maternal 7 trials; not re- RR 1.03, 95% CI 0.94 to 1.12, no evidence of Moderate
vertEn- anaemia ported a difference
abled=false#REF-Bhut- in the third
ta-2012 trimester
Is it time to re-
place iron fo-
late supple-
ments in preg-
nancy with
multiple mi-
cronutrients?
https:// Calcium sup- Maternal 1 trial; 1098 RR 1.04, 95% CI 0.90 to 1.22, no evidence of Not assessed
plementation anaemia women a difference
#/498917022710493686/
versus place-
dash- bo or no treat-
board/htm- ment
lView/2.175.57?re-
vertEn-
abled=false#REF-Bup-
pasiri-2015
(Review)
Informed decisions.
Calcium sup-
plementation
(other than for
preventing or
treating hyper-
tension) for im-
proving preg-
nancy and in-
fant outcomes
https:// IV iron versus Hb 6 trials; num- Significant increase in Hb in the IV group Not assessed
oral iron sup- ber of partici- compared with the oral group in 2 trials
#/498917022710493686/
plementation pants: not re-
dash- in pregnant ported
board/htm- women with
lView/2.175.57?re- IDA
vertEn-
abled=false#REF-Daru-2016
IM versus oral Hb 1 trial; num- No evidence of a difference Not assessed
iron supple- ber of partici-
Systematic re- mentation pants: not re-
view of ran- in pregnant ported
domized tri- women with
als of the effect IDA
of iron supple-
mentation on
IV versus IM Hb 1 trial; num- Significant change in Hb in the IV group Not assessed
iron stores and
iron supple- ber of partici- compared with the IM group
oxygen carry-
mentation pants: not re-
ing capacity in
in pregnant ported
pregnancy
women with
IDA
Weekly oral Hb 3 trials; num- Significant increase in Hb in daily arm in 1 Not assessed
iron supple- ber of partici- trial
mentation pants: not re-
versus daily ported
in pregnant
women with
IDA
Different dos- Hb 2 trials; num- Significant change in Hb in the higher-dose Not assessed
es of oral iron ber of partici- arm in 1 trial
supplementa- pants: not re-
tion in preg- ported
nant women
with IDA
Alternative Hb 3 trials; num- No evidence of a difference Not assessed

oral prepara- ber of partici-
tions versus pants: not re-
a commonly ported
used prepara-
tion in preg-
nant women
with IDA
Oral iron sup- Hb 6 trials; num- Significant increase in Hb in the supple- Not assessed
plementation ber of partici- mented group compared with the placebo
versus place- pants: not re- group in 2 trials
bo in preg- ported
nant women
(Review)
Informed decisions.
with IDA or
NAID
https:// Lipid-based Anaemia 1 trial, 536 RR 2.35, 95% CI 1.67 to 3.30, showing a Moderate
nutrient sup- participants two-fold increase in the prevalence of
#/498917022710493686/
plements anaemia in the LNS group compared to the
dash- (LNS) versus IFA group
board/htm- iron folic acid
lView/2.175.57?re- (IFA) Adverse ef- 1 trial, 881 RR 1.34, 95% CI 0.93 to 1.94 (P = 0.11), did Not assessed
vertEn- fects participants not find any significant difference in hospi-
abled=false#REF-Das-2018 talisation episodes between the LNS and
IFA groups
Lipid-based nu-
trient supple-
Lipid-based Anaemia 1 trial, 557 RR 1.40, 95% CI 1.07 to 1.82, showing in- Moderate
ments for ma-
nutrient sup- participants creased anaemia in the LNS group when
ternal, birth,
plements compared to the MMN group
and infant de-
(LNS) versus
velopmental
multiple mi- Adverse ef- 1 trial, 879 RR 1.18, 95% CI 0.83 to 1.68 (P = 0.36), did Not assessed
outcomes
cronutrients fects participants not find any significant difference in hospi-
(MMN) talisation episodes between the LNS and
MMN groups
https:// Supplementa- Maternal No trials re- No data No data

tion with any anaemia at or ported on this
#/498917022710493686/
folate versus near term (Hb outcome
dash- no interven- <110 g/L at 34
board/htm- tion, placebo weeks' gesta-
lView/2.175.57?re- or other mi- tion or more)
vertEn- cronutrients
abled=false#REF-De_x002d_Regil-2015
without folate
Effects and
safety of peri-
conceptional
oral folate sup-
plementation
for preventing
birth defects
https:// IV iron versus Percentage of 7 trials, partic- OR 2.66, 95% CI 1.71 to 4.15 (P < 0.001), Not assessed
oral iron participants ipants: not re- pregnant women receiving IV iron were
#/498917022710493686/ achieving de- ported more likely to reach their Hb target com-
dash- sired Hb tar- pared with those receiving oral iron
board/htm- get after 4
lView/2.175.57?re- Weeks
vertEn-
abled=false#REF-Govin- Increase in Hb 9 trials, partic- WMD 0.84, 95% CI 0.59 to 1.09 (P < 0.001), Not assessed
dappagari-2019 after 4 weeks ipants: not re- Hb increase was greater in subjects receiv-
of treatment ported ing IV compared with oral iron
Treatment of
iron deficiency
Adverse ef- 11 trials, par- OR 0.35, 95% CI 0.18 to 0.67 (P < 0.001), Not assessed
anemia in preg-
fects in re- ticipants: not women receiving IV iron experienced sig-
nancy with in-
sponse to reported nificantly fewer adverse events compared
travenous ver-
treatment with those receiving oral iron
sus oral iron:
systematic re-
view and meta-
analysis
(Review)
Informed decisions.
https:// MMN supple- Maternal 4 trials; num- RR 1.03, 95% CI 0.87 to 1.22, no evidence of High
mentation anaemia in ber of partici- a difference
#/498917022710493686/
versus iron or third trimester pants: not re-
dash- folate supple- ported
board/htm- mentation
lView/2.175.57?re-
vertEn-
abled=false#REF-Haider-2011
Effect of multi-
ple micronutri-
ent supplemen-
tation during
pregnancy on
maternal and
birth outcomes
https:// Iron, with or Hb (g/L) 8 trials; num- WMD −0.23, 95% CI −12.18 to 11.72, no evi- Not assessed
without folic in second ber of partici- dence of a difference
#/498917022710493686/
acid trimester pants: not re-
dash- ported
board/htm-
lView/2.175.57?re- Hb (g/L) in 36 trials; num- WMD 4.59, 95% CI 3.72 to 5.46 (P <0.001), Not assessed
vertEn- third trimester ber of partici- significantly higher mean Hb concentra-
abled=false#REF-Haider-2013 or at delivery pants: not re- tion for women receiving iron, with or with-
ported out folic acid
Anaemia, pre-
natal iron use,
Hb (g/L) in 12 trials; num- WMD 6.79, 95% CI 0.22 to 13.36, signifi- Not assessed
and risk of ad-
postpartum ber of partici- cantly higher mean Hb concentration for
verse pregnan-
period pants: not re- women receiving iron, with or without folic
cy outcomes:
ported acid
systematic re-
view and meta-
analysis Anaemia in 20 trials; num- RR 0.50, 95% CI 0.42 to 0.59 (P < 0.001), sig- Not assessed
third trimester ber of partici- nificant reduction in anaemia for women
or at delivery pants: not re- receiving iron, with or without folic acid
ported
IDA in third 6 trials; num- RR 0.40, 95% CI 0.26 to 0.60 (P < 0.001), sig- Not assessed
trimester or at ber of partici- nificant reduction in IDA for women receiv-
delivery pants: not re- ing iron, with or without folic acid
ported
ID in third 8 trials; num- RR 0.59, 95% CI 0.44 to 0.79 (P < 0.001), sig- Not assessed
trimester or at ber of partici- nificant reduction in ID for women receiv-
delivery pants: not re- ing iron, with or without folic acid
ported
Iron only ver- Hb (g/L) in 31 trials; num- WMD 4.50, 95% CI 3.62 to 5.39, significantly Not assessed
sus no iron or third trimester ber of partici- higher mean Hb concentration for women
placebo or at delivery pants: not re- receiving iron only
ported
Hb (g/L) in 8 trials; num- WMD 7.01, 95% CI 0.36 to 13.66, signifi- Not assessed
postpartum ber of partici- cantly higher mean Hb concentration for
period pants: not re- women receiving iron only
ported
(Review)
Informed decisions.
Anaemia in 17 trials; num- RR 0.56, 95% CI 0.48 to 0.65, significant re- Not assessed
third trimester ber of partici- duction in anaemia for women receiving
or at delivery pants: not re- iron only
ported
IDA in third 5 trials; num- RR 0.37, 95% CI 0.23 to 0.60, significant re- Not assessed
trimester or at ber of partici- duction in IDA for women receiving iron on-
delivery pants: not re- ly
ported
ID in third 8 trials; num- RR 0.59, 95% CI 0.44 to 0.79, significant re- Not assessed
trimester or at ber of partici- duction in ID for women receiving iron only
delivery pants: not re-
ported
Iron with folic Hb (g/L) in 9 trials; num- WMD 10.41, 95% CI 5.36 to 15.46, signifi- Not assessed
acid versus no third trimester ber of partici- cantly higher mean Hb concentration for
iron and folic or at delivery pants: not re- women receiving iron with folic acid
acid or place- ported
bo
Anaemia in 5 trials; num- RR 0.44, 95% CI 0.37 to 0.53, significant re- Not assessed
third trimester ber of partici- duction in anaemia for women receiving
or at delivery pants: not re- iron with folic acid
ported
https:// Iron versus no Anaemia at 18 trials/qua- RR 0.31, 95% CI 0.22 to 0.44 (P <0.00001), Moderate
iron term si-trials; 8665 significant reduction in anaemia for
#/498917022710493686/ women women receiving iron
dash-
board/htm- Severe 11 trials; num- RR 4.83, 95% CI 0.23 to 99.88, no evidence Not assessed
lView/2.175.57?re- anaemia at ber of partici- of a difference
vertEn- term pants: not re-
abled=false#REF-Im- ported (on-
dad-2012 ly 1 trial con-
tributed data,
Routine iron/ zero events in
folate supple- the rest of the
mentation dur- trials)
ing pregnancy:
effect on ma-
Severe 13 trials; num- RR 0.25, 95% CI 0.03 to 2.48, no evidence of Not assessed
ternal anaemia
anaemia at ber of partici- a difference
and birth out-
any time dur- pants: not re-
comes
ing second or ported
third trimester
IDA at term 7 trials; num- RR 0.44, 95% CI 0.28 to 0.68, significant re- Not assessed
ber of partici- duction in IDA for women receiving iron
pants: not re-
ported
https:// MMN with iron Maternal 9 trials; 5912 RR 1.04, 95% CI 0.94 to 1.15, no evidence of Not assessed
and folic acid anaemia participants a difference
#/498917022710493686/
versus iron (third
dash- with or with- trimester Hb <
board/htm- out folic acid 110 g/L)
lView/2.175.57?re-
vertEn- MMN with iron Maternal 1 trial; num- RR 0.66, 95% CI 0.51 to 0.85 (P = 0.001), sig- Not assessed
abled=false#REF-Keats-2019
and folic acid anaemia ber of partici- nificant reduction in maternal anaemia for
(third
(Review)
Informed decisions.
Multiple-mi- versus place- trimester Hb < pants: not re- women receiving MMN with iron and folic
cronutrient bo 110 g/L) ported acid versus placebo
supplementa-
tion for women
during preg-
nancy
https:// Folic acid ver- Mean pre-de- 12 trials; 1806 MD −0.03, 95% CI −0.25 to 0.19, no evi- Not assessed
sus no folic livery Hb (g/L) participants dence of a difference
#/498917022710493686/
acid
dash- Pre-delivery 8 trials; 4149 RR 0.62, 95% CI 0.35 to 1.10, no evidence of Not assessed
board/htm- anaemia participants a difference
lView/2.175.57?re-
vertEn-
abled=false#REF-Las-
si-2013
Folic acid sup-

plementation
during preg-
nancy for ma-
ternal health
and pregnancy
outcomes
https:// Vitamin A Maternal 3 trials; 3818 RR 0.64, 95% CI 0.43 to 0.94 (P = 0.025), sig- Moderate
alone versus anaemia participants nificant reduction in maternal anaemia for
#/498917022710493686/
placebo or no women receiving vitamin A alone
dash- treatment
board/htm- Neonatal 1 trial; 406 RR 0.99, 95% CI 0.92 to 1.08, no evidence of Not assessed
lView/2.175.57?re- anaemia neonates a difference
vertEn-
abled=false#REF-Mc-Vitamin A Maternal 3 trials; 706 RR 0.86, 95% CI 0.68 to 1.09, no evidence of Low
Cauley-2015 with other anaemia women a difference
micronutri-
Vitamin A sup-
ents versus Neonatal 2 trials; 1052 RR 0.75, 95% CI 0.38 to 1.51, no evidence of Not assessed
plementation
micronutrient anaemia neonates a difference
during preg-
supplements
nancy for ma-
without vita-
ternal and new-
min A
born outcomes
https:// Any supple- Maternal Hb 19 trials; 3704 MD 8.88, 95% CI 6.96 to 10.80 (P < 0.001), Not assessed
ments con- concentra- women significant increase in Hb concentration for
#/498917022710493686/
taining iron tion at or near women receiving daily iron
dash- versus same term (g/L)
board/htm- supplements
lView/2.175.57?re- without iron Maternal Hb 7 trials; 956 MD 7.61, 95% CI 5.50 to 9.72 (P < 0.001), sig- Not assessed
vertEn- or no treat- concentra- women nificant increase in Hb concentration for
abled=false#REF-Pe_x00f1_a_x002d_Rosas-2015a
ment or place- tion within 6 women receiving daily iron
bo (no iron or weeks post-
Daily oral iron placebo) partum (g/L)
supplemen-
tation during
Maternal 14 trials; 2199 RR 0.30, 95% CI 0.19 to 0.46 (P < 0.001), sig- Low
pregnancy
anaemia at women nificant reduction in maternal anaemia for
term (or near women receiving daily iron
term)
(Review)
Informed decisions.
Moderate 3 trials; 766 RR 0.55, 95% CI 0.12 to 2.51, no evidence of Not assessed
anaemia at women a difference
postpartum
Maternal IDA 6 trials; 1088 RR 0.33, 95% CI 0.16 to 0.69 (P = 0.003), Not assessed
at term (or women significant reduction in maternal IDA for
near term) women receiving daily iron
Maternal ID at 7 trials; 1256 RR 0.43, 95% CI 0.27 to 0.66 (P < 0.001), Low
term (or near women significant reduction in maternal ID for
term) women receiving daily iron
Maternal se- 9 trials; 2125 RR 0.22, 95% CI 0.01 to 3.20, no evidence of Very low
vere anaemia women a difference
at any time
during sec-
ond and third
trimester
Maternal se- 8 trials; 1819 RR 0.47, 95% CI 0.01 to 44.11, no evidence Not assessed
vere anaemia women of a difference
at or near
term
Severe 8 trials; 1339 RR 0.04, 95% CI 0.01 to 0.28 (P < 0.001), sig- Not assessed
anaemia at women nificant reduction of severe anaemia post-
postpartum partum for women receiving daily iron
Side effects 11 trials; 2423 RR 1.29, 95% CI 0.83 to 2.02, no evidence of Very low
women a difference
Diarrhoea 3 trials; 1088 RR 0.55, 95% CI 0.32 to 0.93 (P = 0.025), sig- Not assessed
women nificant reduction in diarrhoea for women
receiving daily iron
Constipation 4 trials; 1495 RR 0.95, 95% CI 0.62 to 1.43, no evidence of Not assessed
women a difference
Vomiting 4 trials; 1392 RR 0.88, 95% CI 0.59 to 1.30, no evidence of Not assessed
women a difference
Any supple- Maternal Hb 3 trials; 140 MD 16.13, 95% CI 12.74 to 19.52 (P < 0.001), Not assessed
ments con- concentra- women significant increase in Hb concentration for
taining iron tion at or near women receiving daily iron and folic acid
and folic acid term (g/L)
versus same
supplements Maternal Hb 2 trials; 459 MD 10.07, 95% CI 7.33 to 12.81 (P < 0.001), Not assessed
without iron concentra- women significant increase in Hb concentration for
nor folic acid tion within 6 women receiving daily iron and folic acid
(no iron nor weeks post-
folic acid or partum (g/L)
placebo)
Maternal 3 trials; 346 RR 0.34, 95% CI 0.21 to 0.54 (P < 0.001), sig- Moderate
term (or near women receiving daily iron and folic acid
term)
(Review)
Informed decisions.
Moderate 3 trials; 491 RR 0.33, 95% CI 0.17 to 0.65 (P < 0.001), sig- Not assessed
postpartum women receiving daily iron and folic acid
Maternal IDA 1 trial; 131 RR 0.43, 95% CI 0.17 to 1.09, no evidence of Not assessed
at term (or women a difference
near term)
Maternal ID at 1 trial; 131 RR 0.24, 95% CI 0.06 to 0.99 (P = 0.049), sig- Low
term (or near women nificant reduction in ID for women receiv-
term) ing daily iron and folic acid
Maternal se- 4 trials; 506 RR 0.12, 95% CI 0.02 to 0.63 (P = 0.012), Very low
vere anaemia women significant reduction in maternal severe
at any time anaemia for women receiving daily iron
during sec- and folic acid
ond and third
trimester
Maternal se- 3 trials; 191 RR 0.14, 95% CI 0.01 to 2.63, no evidence of Not assessed
vere anaemia women a difference
at or near
term
Severe 3 trials; 491 RR 0.05, 95% CI 0.00 to 0.76 (P = 0.031), sig- Not assessed
anaemia at women nificant reduction in severe anaemia at
postpartum postpartum for women receiving daily iron
and folic acid
Side effects 1 trial; 456 RR 44.32, 95% CI 2.77 to 709.09 (P = 0.007), Moderate
women significant increase in side effects for
women receiving daily iron and folic acid
https:// Any intermit- Maternal Hb 8 trials; 1306 MD −2.57, 95% CI −5.18 to 0.04, no evi- Not assessed
tent iron regi- (g/L) at or women dence of a difference
#/498917022710493686/
men (with or near term
dash- without oth-
board/htm- er vitamins Maternal 4 trials; 676 RR 1.22, 95% CI 0.84 to 1.80, no evidence of Very low
lView/2.175.57?re- and minerals) anaemia at women a difference
vertEn- versus daily term
abled=false#REF-Pe_x00f1_a_x002d_Rosas-2015b
regimen (with
same vitamins Maternal 8 trials; 1385 RR 1.66, 95% CI 1.09 to 2.53 (P = 0.017), Not assessed
Intermittent and minerals) anaemia at or women increase in anaemia at or near term for
oral iron sup-
near term women receiving intermittent iron
plementation
during preg-
nancy Moderate 9 trials; 1291 RR 2.50, 95% CI 0.84 to 7.48, no evidence of Not assessed
any time dur-
ing second
and third
trimester
Maternal IDA 1 trial; 156 RR 0.71, 95% CI 0.08 to 6.63, no evidence of Very low
at term women a difference
Maternal IDA 2 trials; 278 RR 2.06, 95% CI 0.65 to 6.61, no evidence of Not assessed
at term or women a difference
near term
(Review)
Informed decisions.
Maternal ID at 3 trials; 587 RR 2.38, 95% CI 1.30 to 4.36 (P = 0.005), in- Not assessed
or near term women crease in ID at or near term for women re-
ceiving intermittent iron
Severe 6 trials; 1240 RR 0.00, 95% CI 0.0 to 0.0, no events Very low
anaemia at women
any time dur-
ing second
and third
trimester
Severe 6 trials; 1050 RR 0.00, 95% CI 0.0 to 0.0, no events Not assessed
anaemia at or women
near term
Severe 3 trials; 475 RR 0.00, 95% CI 0.0 to 0.0, no events Not assessed
anaemia at women
term
Severe 1 trial; 169 RR 0.43, 95% CI 0.04 to 4.64, no evidence of Not assessed
postpartum
Side effects 11 trials; 1777 RR 0.56, 95% CI 0.37 to 0.84 (P 0.006), Very low
women significant reduction in side effects for
women receiving intermittent iron
Diarrhoea 5 trials; 613 RR 0.80, 95% CI 0.32 to 2.00, no evidence of Not assessed
women a difference
Constipation 6 trials; 733 RR 0.85, 95% CI 0.45 to 1.59, no evidence of Not assessed
women a difference
Vomiting 6 trials; 954 RR 1.30, 95% CI 0.79 to 2.15, no evidence of Not assessed
women a difference
https:// IV IPM, IS and Hb (g/L) IS (2635 preg- All IV preparations resulted in significant Not assessed
FCM versus nant women; improvements in haematological parame-
#/498917022710493686/
any other 41 studies), ters, with a median increase of 21.80 g/L at
dash- comparator FCM (276 3 to 4 weeks and 30.10 g/L by delivery
board/htm- pregnant
lView/2.175.57?re- women; 4
vertEn- studies) and
abled=false#REF-Qas- IPM (164 preg-
sim-2018 nant women;
3 studies)
Safety and ef-
ficacy of intra-
venous iron
polymaltose,
iron sucrose
and ferric car-
boxymaltose
in pregnancy: a
systematic re-
view
(Review)
Informed decisions.
https:// IV iron thera- Hb (g/L) 9 trials; 1009 MD 7.40 g/L, 95% CI 3.90 to 10.90, signifi- Low
py versus oral women cant increase in Hb concentration at deliv-
#/498917022710493686/
iron ery for pregnant women receiving IV iron
dash- therapy compared to oral iron supplemen-
board/htm- tation
lView/2.175.57?re-
vertEn- 6 trials; 849 MD −1.00 g/L, 95% CI −4.70 to 2.80, no sig- Low
abled=false#REF-Qas- neonates nificant increase in Hb concentration of
sim-2019 neonates at delivery for pregnant women
receiving IV iron therapy compared to oral
Intravenous iron supplementation
or oral iron
for treating
iron deficiency
anaemia dur-
ing pregnancy:
systematic re-
view and meta-
analysis
https:// IV iron sucrose Antenatal 11 trials, 3460 MD 7.80 lower, 95% CI 10.00 lower to 5.70 High
versus oral haemoglobin pregnant lower, significant increase in Hb concentra-
#/498917022710493686/
iron (g/L) women tion for pregnant women receiving IV iron
dash- sucrose compared to oral iron supplemen-
board/htm- tation
lView/2.175.57?re-
vertEn- Antenatal 9 trials, 1147 MD 6.60 lower, 95% CI 10.40 lower to 2.90 High
abled=false#REF-Rad- haemoglo- pregnant lower, significant increase in Hb concentra-
hika-2019 bin level at 6 women tion at 6 weeks for pregnant women receiv-
weeks (g/L) ing IV IS compared to oral iron supplemen-
Parenteral ver- tation
sus oral iron for
treatment of
Post-partum 8 trials, 1370 MD 8.30 lower, 95% CI 12.50 lower to 4.20 Moderate
iron deficiency
haemoglobin post-partum lower, significant increase in Hb concen-
anaemia during
(g/L) women tration for pregnant women receiving IV IS
pregnancy and
compared to oral iron supplementation
post-partum: a
systematic re-
view Post-partum 3 trials, 234 MD 7.10 lower, 95% CI 26.10 lower to Moderate
haemoglo- post-partum 12.002 higher, no significant increase in
bin level at 6 women Hb concentration at 6 weeks for pregnant
weeks (g/L) women receiving IV IS compared to oral
iron supplementation
https:// Oral iron ver- Hb levels (g/L) 2 trials; 215 MD 13.4, 95% CI 2.7 to 24.2 (P = 0.014), sig- Not assessed
sus placebo women nificant increase in Hb concentration for
#/498917022710493686/ women receiving oral iron
dash-
board/htm- Anaemia 1 trial; 125 RR 0.38, 95% CI 0.26 to 0.55 (P < 0.001), sig- Not assessed
lView/2.175.57?re- during 2nd women nificant reduction in anaemia during 2nd
vertEn- trimester trimester for women receiving oral iron
abled=false#REF-Reveiz-2011
Side effects 1 trial; 51 RR 1.97, 95% CI 0.66 to 5.91, no evidence of Not assessed
Treatments for
women a difference
iron-deficien-
cy anaemia in
pregnancy Nausea and 1 trial; 51 RR 4.5, 95% CI 0.54 to 37.54, no evidence of Not assessed
vomiting women a difference
Constipation 1 trial; 51 RR 1.13, 95% CI 0.32 to 4.01, no evidence of Not assessed

women a difference
(Review)
Informed decisions.
Oral iron plus Hb levels (g/L) 1 trial; 125 MD 13.0, 95% CI 11.1 to 14.9 (P < 0.001), sig- Not assessed
vitamin A ver- women nificant increase in Hb concentration for
sus placebo women receiving oral iron plus vitamin A
Anaemia 1 trial; 125 RR 0.04, 95% CI 0.01 to 0.15 (P < 0.001), sig- Not assessed
during 2nd women nificant reduction in anaemia during 2nd
trimester trimester for women receiving oral iron
plus vitamin A
Controlled-re- Side effects 1 trial; 49 RR 0.96, 95% CI 0.40 to 2.33, no evidence of Not assessed
lease oral iron women a difference
versus regular
oral iron Nausea and 1 trial; 49 RR 0.96, 95% CI 0.27 to 3.41, no evidence of Not assessed

women a difference
IM iron sor- Nausea or 1 trial; 48 RR 0.92, 95% CI 0.06 to 13.87, no evidence Not assessed
bito-citric acid vomiting women of a difference
versus IM dex-
tran
IM iron dex- Nausea or 1 trial; 49 RR 0.57, 95% CI 0.05 to 5.83, no evidence of Not assessed
tran versus IV vomiting women a difference
iron dextran
IM iron sor- Nausea or 1 trial; 51 RR 0.52, 95% CI 0.05 to 5.38, no evidence of Not assessed
bitol citric vomiting women a difference
acid versus IV
iron dextran
IV iron versus Side effects 1 trial; 54 RR 0.75, 95% CI 0.19 to 3.04, no evidence of Not assessed
placebo women a difference
Nausea or 1 trial; 54 RR 0.33, 95% CI 0.01 to 7.84, no evidence of Not assessed


women a difference
IV iron versus Maternal Hb 1 trial; 90 MD 7.50, 95% CI 3.40 to 11.60 (P < 0.001), Not assessed
regular oral at birth (g/L) women significant increase in Hb concentration at
iron birth for women receiving IV iron
Mean mater- 3 trials; 167 MD 4.40, 95% CI 0.50 to 8.20 (P = 0.027), sig- Not assessed
nal Hb at 4 women nificant increase in Hb concentration at 4
weeks (g/L) weeks for women receiving IV iron
Side effects 1 trial; 51 RR 0.38, 95% CI 0.11 to 1.31, no evidence of Not assessed
women a difference
Nausea or 3 trials; 244 RR 0.33, 95% CI 0.15 to 0.74 (P = 0.007), sig- Not assessed
vomiting or women nificant reduction in nausea or vomiting or
epigastric dis- epigastric discomfort for women receiving
comfort IV iron
(Review)
Informed decisions.
Constipation 2 trials; 151 RR 0.11, 95% CI 0.02 to 0.71 (P = 0.020), Not assessed
women significant reduction in constipation for
women receiving IV iron
Diarrhoea 3 trials; 237 RR 0.16, 95% CI 0.03 to 0.86 (P = 0.033), sig- Not assessed
women nificant reduction in diarrhoea for women
receiving IV iron
IV iron versus Side effects 1 trial; 52 RR 0.40, 95% CI 0.12 to 1.37, no evidence of Not assessed
controlled-re- women a difference
lease oral iron
Nausea or 1 trial; 52 RR 0.10, 95% CI 0.01 to 1.82, no evidence of Not assessed
Constipation 1 trial; 52 RR 0.93, 95% CI 0.06 to 14.03, no evidence Not assessed

women of a difference
IM iron sor- Mean mater- 1 trial; 200 MD 5.4, 95% CI 3.0 to 7.8 (P < 0.001), signifi- Not assessed
bitol citric nal Hb at birth women cant increase in Hb concentration at birth
acid versus (g/L) for women receiving IM iron
oral iron
Not anaemic 1 trial; 200 RR 1.23, 95% CI 1.01 to 1.48 (P = 0.035), sig- Not assessed
at term women nificant increase in not anaemic at term for
women receiving IM iron
IM iron dex- Not anaemic 1 trial; 60 RR 11.0, 95% CI 1.51 to 79.96 (P = 0.018), Not assessed
tran versus at 6 weeks women significant increase in not anaemic at 6
oral iron plus (packed cell weeks for women receiving IM iron
vitamin C plus volume >
folic acid 33%)
IM iron sor- Mean Hb at 36 1 trial; 150 MD −2.60, 95% CI −4.80 to −0.40 (P = 0.023), Not assessed
bitol citric weeks (g/L) women significant reduction in mean Hb at 36
acid versus weeks for women receiving IM iron
oral iron plus
folic acid Diarrhoea 1 trial; 150 RR 0.09, 95% CI 0.01 to 1.62, no evidence of Not assessed
women a difference
women a difference
Oral iron dai- Hb level at 4 1 trial; 160 MD 5.40, 95% CI 1.40 to 9.40 (P = 0.008), sig- Not assessed
ly versus oral weeks (g/L) women nificant increase in Hb concentration at 4
iron twice weeks for women receiving oral iron daily
weekly
Hb level at 8 1 trial; 129 MD 11.7, 95% CI 6.7 to 16.7 (P < 0.001), sig- Not assessed
weeks (g/L) women nificant increase in Hb concentration at 8
weeks for women receiving oral iron daily
Hb level at 12 1 trial; 105 MD 12.7, 95% CI 6.8 to 18.6 (P < 0.001), sig- Not assessed
weeks (g/L) women nificant increase in Hb concentration at 12
weeks for women receiving oral iron daily
Hb level at 16 1 trial; 102 MD 3.00, 95% CI −0.10 to 6.10, no evidence Not assessed
weeks (g/L) women of a difference
Oral iron dai- Hb level at 16 1 trial; 97 MD 7.00, 95% CI 3.60 to 10.40 (P < 0.001), Not assessed
ly versus oral weeks (g/L) women significant increase in Hb concentration
(Review)
Informed decisions.
iron once at 16 weeks for women receiving oral iron
week daily
Oral iron twice Hb level at 16 1 trial; 101 MD 4.00, 95% CI 0.30 to 7.70 (P = 0.035), sig- Not assessed
a week versus weeks (g/L) women nificant increase in Hb concentration at 16
oral iron once weeks for women receiving oral iron twice
a week a week
IV iron sucrose Hb level at de- 1 trial; 35 MD 5.00, 95% CI −1.80 to 11.80, no evi- Not assessed
500 mg versus livery (g/L) women dence of a difference
IV iron sucrose
200 mg
IV iron sucrose Maternal 1 trial; 40 MD 16.0, 95% CI 8.7 to 23.3 (P < 0.001), sig- Not assessed
500 mg versus haemoglobin women nificant increase in Hb concentration at
IM iron sor- level at birth birth for women receiving IV iron sucrose
bitol (g/L) 500 mg
IV iron sucrose Hb level at de- 1 trial; 45 MD 11.00, 95% CI 4.90 to 17.10 (P < 0.001), Not assessed
200 mg versus livery (g/L) women significant increase in Hb concentration at
IM iron sor- birth for women receiving IV iron sucrose
bitol 200 mg
Oral iron poly- Hb level at 8 1 trial; 100 MD −0.50, 95% CI −3.00 to 2.00, no evi- Not assessed
maltose com- weeks (g/L) women dence of a difference
plex (100 mg)
versus ferrous Constipation 1 trial; 100 RR 0.30, 95% CI 0.14 to 0.64 (P = 0.002), Not assessed
sulphate (120 at 8 weeks women significant reduction in constipation at 8
mg) weeks for women receiving oral iron poly-
maltose complex
Diarrhoea 1 trial; 100 RR 0.22, 95% CI 0.01 to 4.39, no evidence of Not assessed
women a difference
Oral bovine Mean Hb lev- 1 trial; 97 MD −3.00, 95% CI −5.20 to −0.80 (P = 0.008), Not assessed
lactoferrin els at 1 month women significant decrease in Hb concentration
versus ferrous (g/L) at birth for women receiving oral bovine
sulphate lactoferrin
Ferrous sul- Hb level at 8 1 trial; 114 MD −3.00, 95% CI −7.40 to 1.40, no evi- Not assessed
phate (ele- weeks (or un- women dence of a difference
mentary iron) til birth) (g/L)
20 mg versus
40 mg Rate of 1 trial; 114 RR 1.45, 95% CI 0.84 to 2.52, no evidence of Not assessed
anaemia at 8 women a difference
weeks
Rate of mod- 1 trial; 114 RR 1.66, 95% CI 0.58 to 4.76, no evidence of Not assessed
erate anaemia women a difference
at 8 weeks
Vomiting at 8 1 trial; 120 RR 0.71, 95% CI 0.39 to 1.30, no evidence of Not assessed
weeks women a difference
Ferrous sul- Hb level at 8 1 trial; 110 MD −8.00, 95% CI −12.70 to −3.30 (P < Not assessed
phate (ele- weeks women 0.001), significant reduction in Hb level at 8
mentary iron) (or until birth) weeks for women receiving 20 mg ferrous
20 mg versus (g/L) sulphate
80 mg
(Review)
Informed decisions.
Rate of pa- 1 trial; 110 RR 1.56, 95% CI 0.87 to 2.79, no evidence of Not assessed
tients with women a difference
anaemia at 8
weeks
at 8 weeks
Vomiting at 8 1 trial; 119 RR 0.53, 95% CI 0.30 to 0.93 (P = 0.027), sig- Not assessed
weeks women nificant reduction in vomiting at 8 weeks
for women receiving 20 mg ferrous sul-
phate
Ferrous sul- Hb level at 8 1 trial; 112 MD −5.00, 95% CI −9.30 to −0.70 (P = 0.022), Not assessed
phate (ele- weeks women significant reduction in Hb level at 8 weeks
mentary iron) (or until birth) for women receiving 40 mg ferrous sul-
40 mg versus (g/L) phate
80 mg
Rate of pa- 1 trial; 110 RR 1.56, 95% CI 0.87 to 2.79, no evidence of Not assessed
tients with women a difference
anaemia at 8
weeks
at 8 weeks
Vomiting at 8 1 trial; 121 RR 0.75, 95% CI 0.46 to 1.21, no evidence of Not assessed
weeks women a difference
IV iron plus Mean pre-de- 1 trial; 183 MD 4.80, 95% CI 2.10 to 7.50 (P < 0.001), sig- Not assessed
oral iron ver- livery mater- women nificant increase in Hb level at 8 weeks for
sus oral iron nal Hb (g/L) women receiving IV iron
Mean mater- 1 trial; 112 MD 3.90, 95% CI 0.20 to 7.60 (P = 0.037), sig- Not assessed
nal Hb after women nificant reduction in Hb level at 8 weeks for
delivery (g/L) women receiving IV iron
https:// Vitamin C sup- Maternal Hb No trials re- No data Not assessed

plementation ported on the
#/498917022710493686/
alone or in outcome
dash- combination
board/htm- with other Maternal No trials re- No data Not assessed
lView/2.175.57?re- supplements anaemia ported on the
vertEn- outcome
abled=false#REF-Rum-
bold-2015 Side effects of 1 trial; 707 RR 1.16, 95% CI 0.39 to 3.41, no evidence of Not assessed
supplementa- women a difference
Vitamin C sup-
tion: 'any side
plementation
effect'
in pregnancy
Side effects of 1 trial; 1877 RR 1.66, 95% CI 1.16 to 2.37 (P = 0.006), Not assessed
supplementa- women significant increase in abdominal pain for
tion: 'abdomi- women receiving vitamin C supplementa-
nal pain' tion
(Review)
Informed decisions.
https:// IV iron versus Maternal 6 trials; 576 MD 8.50, 95% CI 3.10 to 13.90 (P = 0.002), Not assessed
oral iron haemoglo- women significant increase in Hb concentration for
#/498917022710493686/ bin (g/L) level women receiving IV iron
dash- at the end of
board/htm- treatment
lView/2.175.57?re-
vertEn- Adverse 4 trials; 439 RR 0.50, 95% CI 0.34 to 0.73 (P < 0.001), sig- Not assessed
abled=false#REF-Shi-2015 events at the women nificant reduction in adverse events for
end of treat- women receiving IV iron
Intravenous ment
iron sucrose
versus oral iron
in the treat-
ment of preg-
nancy with
iron deficiency
anaemia: a sys-
tematic review
https:// Vitamin A ver- Hb (g/L) 6 trials; 1034 MD 3.50, 95% CI 2.40 to 4.50 (P < 0.001), sig- Moderate
sus placebo or pregnant nificant increase in Hb concentration for
#/498917022710493686/
multivitamins women pregnant women receiving vitamin A sup-
dash- plementation
board/htm-
lView/2.175.57?re- Anaemia 6 trials; 1587 RR 0.81, 95% CI 0.69 to 0.94 (P = 0.007), sig- High
vertEn- pregnant nificant reduction in anaemia for pregnant
abled=false#REF-Thorne_x002d_Ly- women women receiving vitamin A supplementa-
man-2012 tion
Vitamin A and
Severe 2 trials; 961 RR 0.93, 95% CI 0.59 to 1.45, no evidence of Low
carotenoids
anaemia pregnant a difference
during preg-
women
nancy and ma-
ternal, neona-
tal and infant
health out-
comes: a sys-
tematic re-
view and meta-
analysis
Fortification
https:// Non-dairy Hb 1 trial; 439 Significant improvement in Hb (P = 0.015) Not assessed

MMN-fortified pregnant in the intervention group compared with
#/498917022710493686/
beverages ver- women the control group
dash- sus iso-caloric
board/htm- non-fortified
lView/2.175.57?re- beverage
vertEn-
abled=false#REF-Aaron-2015
Multiple-mi-
cronutrient for-
tified non-dairy
beverage in-
terventions re-
duce the risk
of anemia and
iron deficien-
(Review)
Informed decisions.
cy in school-
aged children
in low-middle
income coun-
tries: a system-
atic review and
meta-analysis
https:// MNP for point- Hb concentra- 1 trial; 405 MD −2.50, 95% CI −4.85 to −0.15 (P = 0.037), Not assessed
of-use for- tion (g/L) at 32 women significant reduction in Hb concentration
#/498917022710493686/
tification of weeks’ gesta- for women receiving MNP-fortified food
dash- foods versus tion
board/htm- iron and folic
lView/2.175.57?re- acid supple- Any anaemia 1 trial; 405 RR 1.25, 95% CI 1.00 to 1.57 (P = 0.047), sig- Not assessed
vertEn- ments at 32 weeks’ women nificant increase in anaemia for women re-
abled=false#REF-Suchdev-2015 gestation ceiving MNP fortified food
Multiple mi-
MNP for point- Maternal Hb 1 trial; 470 MD 1.00, 95% CI −1.77 to 3.77, no evidence Not assessed
cronutrient
of-use for- (g/L) at term women of a difference
powders for
tification of or near term
home (point-
foods versus
of-use) fortifi-
same multi- Maternal 1 trial; 470 RR 0.92, 95% CI 0.53 to 1.59, no evidence of Very low
cation of foods
ple micronu- anaemia at women a difference
in pregnant
trients in sup- term or near
women
plements term
CI: confidence interval; FCM: ferric carboxymaltose; Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; IM: intramuscular;
IPM: iron polymaltose; IS: iron sucrose; IV: intravenous; MD: mean difference; MMN: multiple micronutrient; MNP: micronutrient powders;
OR: odds ratio; RR: risk ratio; SMD: standardised mean difference.
Table 26. Results of included systematic reviews: mixed populations

ber of partici-
pants
Supplementation
Arabi 2020 Vitamin D sup- Hb (g/L) 1 trial, 205 SMD 0.13, 95% CI -0.16 to 0.42 (P = 0.38), vi- Not assessed
plements ver- healthy tamin D supplementation leads to a non-
The effect of vi- sus control adults; significant reduction in haemoglobin lev-
tamin D sup- els;
plementation 2 trials, 466
on hemoglobin anaemic pa- SMD 0.02, 95% CI −0.20 to 0.24 (P = 0.84),
concentration: tients vitamin D supplementation leads to a non-
a systematic re- significant reduction in haemoglobin levels
view and meta-
analysis Ferritin 3 trials, 303 SMD −0.17, 95% CI −0.72 to 0.39 (P = 0.56) Not assessed
healthy
adults; SMD −0.18, 95% CI −0.36 to 0.01 (P = 0.06)
2 trials, 466
anaemic pa-
tients
Basutkar 2019 Vitamin D sup- Hb (g/L) 4 trials, 407 MD −0.05, 95% CI −0.39 to 0.28 (P < 0.18), vi- High
plementation participants tamin D supplementation had no statisti-
(Review)
Informed decisions.
Table 26. Results of included systematic reviews: mixed populations (Continued)

Vitamin D sup- versus control cally significant impact on the outcomes of
plementation groups admin- haemoglobin
in patients with istered place-
iron deficiency bo Ferritin 3 trials, 396 MD 1.70, 95% CI −9.12 to 12.53 (P < 0.21), High
anaemia: A sys- participants Vitamin D supplementation had no statisti-
tematic review cally significant impact on the outcomes of
and a meta- serum ferritin
analysis
Casgrain 2012 Iron supple- Hb (g/L) 37 trials, 49 MD 5.10, 95% CI 3.70 to 6.50 (P < 0.001), sig- Not assessed
mentation arms; 3577 nificant increase in Hb concentration for
Effect of iron versus place- participants participants receiving iron supplementa-
intake on iron bo or control tion
status: a sys-
tematic re-
view and meta-
analysis of ran-
domized con-
trolled trials
Gera 2007 Iron supple- Hb (g/L) 55 trials; WMD 7.40, 95% CI 6.10 to 8.70 (P < 0.001), Not assessed
mentation 12,198 partici- significant increase in Hb concentration for
Effect of iron versus place- pants children receiving iron supplementation
supplementa- bo
tion on haemo-
globin response
in children: sys-
tematic review
of randomised
controlled trials
Gera 2009 Iron and mul- Hb (g/L) 23 trials; 4981 WMD 6.50, 95% CI 5.00 to 8.00 (P < 0.001), Not assessed
tiple micronu- participants significant increase in Hb concentration
Effect of com- trient supple- for children receiving iron and multiple mi-
bining multiple mentation cronutrients versus placebo or no treat-
micronutrients versus place- ment
with iron sup- bo or no treat-
plementation ment
on Hb response
in children: sys- Iron and mul- Hb (g/L) 13 trials; 1483 WMD 1.40, 95% CI 0.00 to 2.80 (P = 0.044), Not assessed
tematic review tiple-micronu- participants significant increase in Hb concentration
of randomized trient supple- for children receiving iron and multiple mi-
controlled trials mentation cronutrients versu2`s iron alone
versus iron
supplementa-
tion
Silva 2018 Children: di- Hb (g/L) Iron status: MD 3.19, 95% CI 1.31 to 5.07 (P < 0.001), sig- Not assessed
etary inter- anaemia or nificant increase in Hb concentration for
Effects of iron vention versus deficient = 3 children with anaemia or iron deficiency
supplementa- iron supple- trials; 425 chil- anaemia receiving supplementation
tion versus di- mentation dren
etary iron on
the nutrition-
al iron status:
systematic re- Iron status: MD −6.58, 95% CI −11.52 to −1.64 (P = Not assessed
view with meta- non-anaemia 0.009), significant reduction in Hb concen-
analysis of ran- or sufficient tration for non-anaemic children receiving
domized con- = 3 trials; 305 dietary intervention
trolled trials children
(Review)
Informed decisions.
Final preva- 3 trials; num- 3 trials reported final anaemia prevalence Not assessed
lence of ber of partici- after supplementation versus fortification:
anaemia pants: not re- 4.3% versus 9.7%, 42.5% versus 54.9%, and
ported 6.6% versus 9.7%
Adolescents Hb (g/L) 5 trials; 165 MD 0.04, 95% CI −2.50 to 2.58, no evidence Not assessed
and adults: di- participants of a difference
etary plan ver-
sus iron sup-
plement only
Pregnant Hb (g/L) 1 trial; num- 113.3 (± 8.8) for supplementation versus Not assessed
women: di- ber of partici- 112.1 (± 8.4) for fortified food, significant
etary plan ver- pants: not re- increase in Hb for pregnant women receiv-
sus iron supported ing supplementation
plement only
Smelt 2018 Vitamin B12 Hb (g/L) 4 trials; 343 MD 0.00, 95% CI −0.19 to 0.18, no evidence Not assessed
supplemen- participants of a difference
The effect of tation versus
vitamin B12 placebo
and folic acid
supplementa- Folic acid sup- Hb (g/L) 3 trials; 929 MD −0.09, 95% CI −0.19 to 0.01, no evi- Not assessed
tion on routine plementation participants dence of a difference
haematological versus place-
parameters in bo
older people:
an individual
participant da-
ta meta-analy-
sis
Tay 2015 Oral iron sup- Hb (g/L) 3 trials; 438 el- MD 3.50, 95 % CI 1.20 to 5.90 (P = 0.003), Not assessed
plementation derly people significant increase in Hb concentration for
Systematic re- versus no oral elderly people taking oral iron
view and meta- supplementa-
analysis: what tion or place- Adverse ef- 3 trials; 440 36 participants with oral iron supplemen- Not assessed
is the evidence bo fects participants tation reported adverse events (constipa-
for oral iron tion, diarrhoea, abdominal pain, indiges-
supplementation, nausea and vomiting)
tion in treating
anaemia in el-
derly people?
Tolkien 2015 Adults, includ- Incidence of 20 trials; 3168 OR 2.32, 95% CI 1.74 to 3.08 (P < 0.0001), Not assessed
ing pregnant GI side effects participants significant increase in the incidence of GI
Ferrous sulfate women: oral side effects for participants receiving oral
supplementa- iron supple- iron versus placebo
tion causes sig- mentation
nificant gas- versus place-
trointestinal bo
side-effects in
adults: a sys- Adults, includ- Hb 20 trials; num- Increase in Hb for oral iron supplementa- Not assessed
tematic re- ing pregnant ber of partici- tion was lower than for IV iron
view and meta- women: oral pants: not re-
analysis iron supple- ported
mentation
versus IV iron Incidence of 23 trials; num- OR 3.05, 95% CI 2.07 to 4.48 (P < 0.0001), Not assessed
GI side effects ber of partici- significant increase in the incidence of GI
(Review)
Informed decisions.

pants: not re- side effects for participants receiving oral
ported iron versus IV iron
Adults, includ- Constipation 27 trials; num- Incidence in the oral iron group was 12%, Not assessed
ing pregnant ber of partici- 95% CI 10% to 15%
women: oral pants: not re-
iron supple- ported
mentation
versus place- Nausea 30 trials; num- Incidence in the oral iron group was 11%, Not assessed
bo or IV iron ber of partici- 95% CI 8% to 14%
pants: not re-
ported
Diarrhoea 25 trials; num- Incidence in the oral iron group was 8%, Not assessed
ber of partici- 95% CI 6% to 11%
pants: not re-
ported
Pregnant Incidence of 5 trials; 561 OR 9.44, 95% CI 2.23 to 39.93 (P = 0.002), Not assessed
women only: GI side effects pregnant increase in the incidence of GI side effects
oral iron sup- women for participants receiving oral iron versus IV
plementation iron
versus place-
bo or IV iron
Fortification
Das 2019b MMN fortifi- Serum Hb lev- 20 trials; 6985 MD 3.01 g/L, 95% CI 2.14 to 3.87 (P < 0.001), Low
cation versus el (g/L) participants significant increase in Hb concentration for
Food fortifica- placebo/no in- participants receiving MMN fortification
tion with mul- tervention
tiple micronu- Anaemia (Hb < 11 trials; 3746 RR 0.68, 95% CI 0.56 to 0.84 (P < 0.001), sig- Low
trients: impact 11 g/dL) participants nificant decrease in anaemia for partici-
on health out- pants receiving MMN fortification
comes in gener-
al population
IDA (Hb < 11 6 trials; 2189 RR 0.28, 95% CI 0.19 to 0.39 (P < 0.001), sig- Low
g/dL with participants nificant decrease in IDA for participants re-
serum ferritin ceiving MMN fortification
< 15 μg/L)
ID (serum fer- 11 trials; 3289 RR 0.44, 95% CI 0.32 to 0.60 (P < 0.001), sig- Low
ritin < 5 μg/L) participants nificant decrease in ID for participants re-
ceiving MMN fortification
Field 2020 Wheat flour Hb (g/L) 7 trials; 2355 MD 3.30 g/L, 95% CI 0.86 to 5.74 (P = 0.008), Very low
fortified with participants significant increase in Hb concentration for
Wheat flour for- iron alone ver- participants receiving fortified flour
tification with sus unfortified
iron for reduc- wheat flour Anaemia 5 trials; 2200 RR 0.81, 95% CI 0.61 to 1.07, no evidence of Low
ing anaemia participants a difference
and improving
iron status in
ID 3 trials; 633 RR 0.43, 95% CI 0.17 to 1.07, no evidence of Moderate
populations
participants a difference
Wheat flour Hb (g/L) 3 trials; 384 MD 3.29 g/L, 95% CI -0.78 to 7.36, no evi- Low
fortified with participants dence of a difference
iron in com-
bination with
other mi-
(Review)
Informed decisions.

cronutrients
Anaemia 2 trials; 322 RR 0.95, 95% CI 0.69 to 1.31, no evidence of Low
versus unforti-
fied wheat
ID 3 trials; 387 RR 0.74, 95% CI 0.54 to 1.00, no evidence of Moderate
Wheat flour Hb (g/L) 2 trials; 488 MD 0.81 g/L, 95% CI -1.28 to 2.89, no evi- Low
fortified with participants dence of a difference
iron in com-
bination with Anaemia 1 trial; 127 RR 0.24, 95% CI 0.08 to 0.71 (P = 0.009), sig- Very low
other mi- participants nificant decrease in anaemia for partici-
cronutrients pants receiving fortified flour
versus forti-
fied wheat ID 1 trial; 127 RR 0.42, 95% CI 0.18 to 0.97 (P = 0.04), sig- Very low
flour with participants nificant decrease in ID for participants re-
same mi- ceiving fortified flour
cronutrients
(but not iron)
Finkelstein Iron-biofor- Anaemia (Hb < 3 trials; 597 OR 0.83, 95% CI 0.58 to 1.19, no evidence of Not assessed
2019 tified staple 120 g/L) participants a difference
crops versus
Iron bioforti- conventional ID (serum fer- 3 trials; 603 OR 0.86, 95% CI 0.61 to 1.23, no evidence of Not assessed
fication inter- crops rin < 15.0 μg/ participants a difference
ventions to im- L)
prove iron sta-
tus and func-
tional out-
comes
Garcia-Casal Maize flour or Hb (g/L) 3 trials; 1144 MD 1.25, 95% CI −2.36 to 4.86, no evidence Very low
2018 maize flour participants of a difference
products forti-
Fortification fied with iron Anaemia 2 trials; 1027 RR 0.90, 95% CI 0.58 to 1.40, no evidence of Very low
of maize flour plus other vi- participants a difference
with iron for tamins and
controlling minerals ver- IDA 1 trial; 515 RR 1.04, 95% CI 0.58 to 1.88, no evidence of Not assessed
anaemia and sus participants a difference
iron deficiency unfortified
in populations maize flours ID 2 trials; 1102 RR 0.75, 95% CI 0.49 to 1.15, no evidence of Very low
or maize flour participants a difference
products (not
containing
iron nor any
other vitamin
and minerals)
Gera 2012 Fortification Hb (g/L) 54 trials (77 WMD 4.20, 95% CI 2.80 to 5.60 (P < 0.001), Not assessed
with iron ver- analytic com- significant increase in Hb concentration for
Effect of iron- sus control ponents); participants receiving fortification
fortified foods 19,161 partici-
on hematologic pants
and biological
outcomes: sys- Anaemia at 33 trials; RR 0.59, 95% CI 0.48 to 0.71 (P < 0.001), sig- Not assessed
tematic review end of fortifi- 13,331 partici- nificant reduction in anaemia for partici-
of randomized cation pants pants receiving fortification
controlled trials
(Review)
Informed decisions.
ID 21 trials; 5765 RR 0.48, 95% CI 0.38 to 0.62 (P < 0.001), sig- Not assessed
participants nificant reduction in ID for participants re-
ceiving fortification
Hess 2016 Fortified Hb (g/L) 13 trials (14 WMD 6.80, 95% CI 5.10 to 8.50, significant Not assessed
condiments comparisons); increase in Hb concentration for partici-
Micronutrient and noo- 8845 participants receiving fortified food
fortified condi- dles versus pants
ments and noo- non-fortified
dles to reduce condiments or Anaemia 10 trials (11 RR 0.59, 95% CI 0.44 to 0.80, significant re- Not assessed
anemia in chil- noodles prevalence comparisons); duction in anaemia for participants receiv-
dren and adults 5498 partici- ing fortified food
—a literature pants
review and
meta-analysis
Huo 2015 NaFeED- Hb (g/L) 12 trials; 8071 MD 8.81 g/L, 95% CI 5.96 to 11.67 (P < Not assessed
TA-fortified participants 0.001), significant increase in Hb concen-
Effect of soy sauce ver- tration for participants receiving fortified
NaFeEDTA-for- sus non-forti- soy sauce
tified soy sauce fied soy sauce
on anemia Anaemia rates 16 trials; OR 0.25, 95% CI 0.19 to 0.35 (P < 0.001), sig- Not assessed
prevalence in 16,819 partici- nificant reduction in anaemia for partici-
China: a sys- pants pants receiving fortified soy sauce
tematic re-
view and meta-
analysis of ran-
domized con-
trolled trials
Peña-Rosas Rice forti- Hb (g/L) 11 trials, 2163 MD 1.83 g/L, 95% CI 0.66 to 3.00, significant Low
2019 fied with iron participants increase in Hb concentration for partici-
alone or in pants consuming rice fortified with iron or
Fortification of combination in combination with other micronutrients
rice with vita- with other mi-
mins and min- cronutrients Anaemia 7 trials, 1634 RR 0.72, 95% CI 0.54 to 0.97, significant re- Low
erals for ad- versus unforti- (WHO cut-off) children duction in anaemia for children consuming
dressing mi- fied rice or no rice fortified with iron or in combination
cronutrient intervention with other micronutrients
malnutrition
ID 8 trials, 1733 RR 0.66, 95% CI 0.51 to 0.84, significant re- Low
participants duction in ID for participants consuming
rice fortified with iron or in combination
with other micronutrients
Diarrhoea 1 trial, 258 RR 0.3.52, 95% CI 0.18 to 67.39, no signif- Very low
children icant reduction in diarrhoea for children
consuming rice fortified with iron or in
combination with other micronutrients
Adverse effect 1 trial, 785 RR 1.78, 95% CI 1.18 to 2.70, significant in- Low
(hookworm participants crease the hookworm infection risk for par-
infection risk) ticipants consuming rice fortified with iron
or in combination with other micronutri-
ents
Adverse ef- 1 trial, 234 RR 0.77, 95% CI 0.42 to 1.42, no significant Not reported
fect (abdomi- children increase the risk of abdominal pain more
nal pain more than three days for children given rice forti-
(Review)
Informed decisions.

than three fied with iron or in combination with other
days) micronutrients
Rice fortified Hb (g/L) 1 trial, 74 par- MD 10.00 g/L, 95% CI 8.79 to 11.21, signifi- Low
with vitamin ticipants cant increase in Hb concentration for par-
A alone or in ticipants receiving rice fortified with vita-
combination min A alone or in combination with other
with other mi- micronutrients
cronutrients
versus unforti-
fied rice or no
intervention
Ramírez- DFS versus Hb (g/L) 14 trials; MD 3.01, 95% CI 1.79 to 4.24 (P < 0.001), Not assessed
Luzuriaga 2018 control salt 45,759 partici- SMD 0.21, 95% CI 0.12 to 0.29 (P < 0.001),
pants significant increase in Hb concentration for
Impact of dou- participants receiving DFS
ble-fortified
salt with iron Anaemia 10 trials; RR 0.84, 95% CI 0.78 to 0.92 (P < 0.001), sig- Not assessed
and iodine on 42,103 partici- nificant reduction in anaemia for partici-
hemoglobin, pants pants receiving DFS
anemia, and
iron deficien-
IDA 4 trials; 831 RR 0.37, 95% CI 0.25 to 0.54 (P < 0.001), sig- Not assessed
cy anemia: a
participants nificant reduction in IDA for participants
systematic re-
receiving DFS
view and meta-
analysis
Sadighi 2019 Iron-fortified Hb (g/L) 46 trials MD 2.63 g/L, 95% CI 1.31 to 3.95 (P < 0.001), Not assessed
flour versus (10,353 in- significant increase in Hb concentration for
Systematic re- control fants/tod- participants receiving iron-fortified flour
view and meta- dlers, chil-
analysis of the dren, women)
effect of iron-
fortified flour Prevalence of 27 trials (6950 MD −0.08 (−8.1 %), 95% CI −0.117 to Not assessed
on iron status anaemia infants/tod- −0.044 (P < 0.001), significant reduction in
of populations dlers, chil- anaemia prevalence for participants re-
worldwide dren, women) ceiving iron-fortified flour
Prevalence of 15 trials (4260 MD −0.209 (−20.9%), 95% CI −0.384 to Not assessed

IDA infants/tod- −0.034 (P = 0.019), significant reduction in
dlers, chil- IDA prevalence for participants receiving
dren, women) iron-fortified flour
Prevalence of 23 trials (5371 MD −0.120 (−12%), 95% CI −0.189 to −0.051 Not assessed
ID infants/tod- (P = 0.001), significant reduction in ID
dlers, chil- prevalence for participants receiving iron-
dren, women) fortified flour
Tablante 2019 Wheat flour Hb g/L 1 trial, 334 MD 0.00 g/L (2.08 lower to 2.08 higher), Low
fortified with children there were no significant effects of fortified
Fortification folic acid and wheat flour flatbread, compared to unforti-
of wheat and other mi- fied wheat flour flatbread, on haemoglobin
maize flour cronutrients concentrations
with folic acid versus unfor-
for popula- tified wheat Anaemia 1 trial, 334 RR 1.07, 95% CI 0.74 to 1.55 (P = 0.72), Low
tion health out- flour children there were no significant effects of fortified
comes wheat flour flatbread, compared to unforti-
fied wheat flour flatbread, on anaemia
(Review)
Informed decisions.
Yadav 2019 Dou- Hb g/L 10 trials MD 4.40, 95% CI 1.60 to 7.10 (P < 0.01), sig- Not assessed
ble‑for- nificant increase in Hb levels for partici-
Meta-analysis tified salt pants consuming DFS
of efficacy of (iron and io-
iron and iodine dine) (DFS) Anaemia 7 trials (1526 Risk difference (RD) −0.16, 95% CI −0.26 to Not assessed
fortified salt in versus iodine participants) −0.06 (P < 0.001), significant risk reduction
improving iron only fortified in anaemia for participants consuming DFS
nutrition status salt (IS)
IDA Not reported RD −0.08, 95% CI −0.28 to 0.11, no evidence Not assessed
of a difference
ID 5 trials (1306 RD −0.20, 95% CI: −0.32 to −0.08 (P < 0.001), Not assessed
participants) significant risk reduction in iron deficiency
for participants consuming DFS
Geerligs 2003 Food pre- Change in Hb 3 trials (784 2 of the 3 trials found a difference in Not assessed
pared in cast concentration participants) haemoglobin at the end of the trial, with
Food prepared iron pots ver- children eating food prepared in iron pots
in iron cook- sus food pre- having a significantly higher haemoglobin.
ing pots as an pared in non-
intervention cast iron pots trial 1: Hb 13 g/L higher in iron pot group
for reducing after 12 months (P < 0.001), Malaria en-
iron deficiency demicity very low
anaemia in de-
veloping coun- trial 2: Hb 13 g/L higher in iron pot group
tries: a system- after 8 months (P = 0.02), Malaria endemic-
atic review ity none
trial 3: Hb 0.2 g/L higher in iron pot group

after 5 months for those aged 1-11 years
(parasite rate 45.3%), Hb 3 g/L higher in
iron pot group after 5 months for those >
12 years of age (parasite rate 17.5%), not
significant
CI: confidence interval; DFS: double-fortified salt; GI: gastrointestinal, Hb: haemoglobin; IS: iodine-fortified salt; IV: intravenous; MD:
mean difference; MMN: multiple micronutrient; OR: odds ratio; RR: risk ratio; SMD: standardised mean difference; WMD: weighted mean
difference.
APPENDICES
Appendix 1. Protocols for future assessment and possible inclusion in this review
Reference Protocol title
An 2020 Effects of probiotics/prebiotics/synbiotics supplementation on iron status and anemia
Andersen 2016 Child iron supplementation or fortification for anemia, growth, infection, and developmental out-
comes: a systematic review and meta-analysis of randomized trials
Butwick 2017 A systematic review of the efficacy of oral versus intravenous iron therapy for the treatment of
postpartum anemia
(Review)
Informed decisions.
(Continued)
Da Rocha 2017 The effects of iron supplementation versus dietary iron on iron reserves in children: a systematic
review and meta-analysis
Dubey 2019 A systematic review and meta-analysis on the effect of food fortification with micronutrients (iron/
folic acid/vitamin B12, or combination) on anemia among pregnant women
Gadhave 2020 Effect of meal supplementation during the antenatal period on the improvement in maternal and
birth weight
Hansen 2020 Benefits and risks of daily oral iron supplementation in pregnancy in iron replete non-anaemic
women: a systematic review
Hare 2018 Health outcomes of iron supplementation and/or food fortification in iron-replete children aged
4-24 months: a systematic review and meta-analysis of randomised controlled trials
Jere 2020 The effects of B vitamins and/or iron on haematological parameters and nutrient biomarkers of
anaemia in children in low- and middle-income countries: a systematic review and meta-analysis
of randomized controlled trials
Moore 2014 A systematic review and meta-analysis of the evidence for the regulation of dietary iron bioavail-
ability by vitamin C and phytate, in the context of hepcidin, and subsequent effects on iron status
Nikooyeh 2018 Nutritional impacts of home-fortification strategies in children younger than 5 year-old: a system-
atic review and meta-analysis
Pasricha 2011 Daily iron supplementation for improving anaemia and health in children
Rahman 2019 Systematic review of randomised controlled trials for effectiveness of intervention for prevention
of anaemia in pregnancy
Rogozinska 2018 Iron treatments (Fe) in reproductive age women with Iron Deficient Anaemia (FRIDA): a systematic
review with network meta-analysis of randomised controlled trials
Rosli 2019 Iron polymaltose complex for iron deficiency anaemia in children
Tsang 2015 Folate supplementation in women of reproductive age
Zamalloa 2017 The impact of counseling and education on incidence rates of anemia and iron deficiency in chil-
dren under 3 years
Zandonadi 2017 Food strategy for the prevention and treatment of iron deficiency anemia in childhood: a systemat-
ic review
Appendix 2. Search strategies

Cochrane Database of Systematic Reviews (CDSR), in the Cochrane Library
#1 [mh anemia]
#2 (anaem* or anem* or non-anemic* or non-anaemic*):ti,ab
#3 (iron* near/3 (deficien* or status)):ti,ab
#4 (haemoglobin or hemoglobin or Hb):ti,ab
#5 (ferric or ferrous or ferritin* or Fe):ti,ab
#6 {or #1-#5}
#7 [mh "Nutrition therapy"]
#8 [mh "Dietary Supplements"]
#9 [mh "Diet Therapy"] or [mh Diet]
#10 [mh Micronutrients]
(Review)
Informed decisions.
#11 [mh "foods, specialized"]

#12 [mh Biofortification]
#13 [mh Iron] or [mh Zinc] or [mh "vitamin A"]
#14 [mh "iron, dietary"]
#15 [mh Lipids]
#16 [mh "Iron Chelating Agents"]
#17 [mh "ferric compounds"] or [mh "ferrous compounds"]
#18 (*nutrient* or nutrition* or diet* or food* or feeding or supplement* or complementary or *fortif* or vitamin):ti,ab
#19 ("point of use" or "ready to use" or RUSF* or RUTF* or FBF*):ti,ab
#20 (iron* or zinc* or "vitamin A" or retinol*):ti,ab
#21 (counsel* or education* or teach* or class*):ti
#22 [mh "health education"] or [mh "health promotion"]
#23 [mh Weaning] or wean*;ti,ab
#24 {or #7-#23}
#25 #6 and #24, in Cochrane Reviews, Cochrane Protocols
#26 #6 and #24 with Cochrane Library publication date Between Jul 2018 and Aug 2020, in Cochrane Reviews, Cochrane Protocols
MEDLINE Ovid
1 exp Anemia/
2 (anaem$ or anem$ or non-anemic$ or non-anaemic$).tw,kf.
3 (iron$ adj3 (deficien$ or status)).tw,kf.
4 (haemoglobin or hemoglobin or Hb).tw,kf.
5 (ferric or ferrous or ferritin$ or Fe).tw,kf.
6 or/1-5
7 exp NUTRITION THERAPY/
8 Dietary Supplements/
9 Micronutrients/
10 exp foods, specialized/
11 diet/
12 food, fortified/
13 Biofortification/
14 iron/ or zinc/ or vitamin A/
15 (nutrition$ or diet$).ti.
16 (micronutrient$ or micro-nutrient$).tw,kf.
17 (multinutrient$ or multi-nutrient$ or multi$ nutrient$).tw,kf.
18 (multimicro-nutrient$ or multimicronutrient$).tw,kw.
19 (MNPs or MMPs or Sprinkles or Vita Shakti or Rahama or Anuka or Chispitas or BabyFer or Bebe Vanyan or Supplefer or Supplefem).tw,kf.
20 (multivitamin$ or multi-vitamin$).tw,kf.
21 (trace adj (element$ or mineral$ or nutrient$)).tw,kf.
22 iron, dietary/
23 Iron Chelating Agents/
24 ferric compounds/ or ferrous compounds/
25 (iron$ or zinc$ or "vitamin A" or retinol$).tw,kf.
26 (folic$ or folate$ or folvite$ or folacin$ or pteroylglutamic$).tw,kf.
27 exp Lipids/
28 (fatty acid$ or Docosahexaenoic acid$ or Eicosapentaenoic Acid$ or PUFA$ or lipid$ or omega 3$ or omega 6$).tw,kf.
29 (soy$ or wheat-soy$ or corn-soy$ or peanut or groundnut or whey or sesame or cashew or chickpea or oil$).tw,kf.
30 ((fortif$ or supplement$) adj3 (blend$ or diet$ or food$ or nutrition$)).tw,kf.
31 ((fortif$ or supplement$) adj3 (cereal$ or condiment$ or flour$ or legume$ or rice$ or salt$ or sauce$ or milk$ or formula)).tw,kf.
32 ("point of use" or point-of-use or "ready to use" or "ready -to- use" or RUSF$1 or RUTF$1) .tw,kf.
33 Weaning/
34 (complementary adj3 (feed$ or food$ or nutrition$)).tw,kf.
35 weaning.tw,kf.
36 (biofortif$ or bio-fortif$).tw,kf.
37 or/7-36
38 6 and 37
39 Anemia, Iron-Deficiency/dh, pc, th [Diet Therapy, Prevention & Control, Therapy]
40 38 or 39
41 Nutritional Sciences/
42 diet/
(Review)
Informed decisions.
43 Diet Therapy/
44 Nutrition Therapy/
45 or/41-44
46 Health Education/
47 Health Knowledge, Attitudes, Practice/
48 health promotion/
49 Counseling/
50 or/46-49
51 45 and 50
52 ((nutrition$ or diet$ or food or feeding) adj3 (counsel$ or education$ or teach$ or class$)).tw,kf.
53 51 or 52
54 6 and 53
55 40 or 54
56 exp animals/ not humans/
57 55 not 56
58 meta-analysis.pt.
59 Meta-Analysis as Topic/
60 systematic$ review$.tw.
61 (metanalysis or metaanalysis or meta analysis).tw.
62 (metaregression or meta-regression or meta regression).tw.
63 (metasynthesis or meta-synthesis or meta synthesis).tw.
64 (realist review or realist synthesis or rapid review or pragmatic review or umbrella review).tw.
65 (Medline or Pubmed or Embase or Cinahl or Cochrane).ab.
66 ((literature or database$ or bibliographic) adj3 search$).ab.
67 ((inclusion or selection or predefined or predetermined) adj5 (studies or articles or reports)).ab.
68 or/58-67
69 57 and 68
70 limit 57 to systematic reviews
71 69 or 70
72 (201807* or 201808* or 201809* or 201810* or 201811* or 201812* or 2019* or 2020*).dt,ez,da.
73 71 and 72
MEDLINE In-Progress and other Non-Indexed Citations Ovid

5 or/1-4
8 (multimicro-nutrient$ or multimicronutrient$).tw,kf.
13 (folic$ or folate$ or folvite$ or folacin$ or pteroylglutamic$).tw,kf. (2861)
17 ((fortif$ or supplement$) adj3 (cereal$ or condiment$ or flour$ or legume$ or rice$ or salt$ or sauce$ or milk$ or formula)).tw,kf.)
18 ("point of use" or point-of-use or "ready to use" or "ready -to- use" or RUSF$1 or RUTF$1 or FBF$1).tw,kf.
20 weaning.tw,kf.
23 or/6-22
24 5 and 23
(Review)
Informed decisions.
33 or/25-32
34 24 and 33
35 (201807* or 201808* or 201809* or 201810* or 201811* or 201812* or 2019* or 2020*).dt,ez,da.
36 34 and 35
MEDLINE Epub Ahead of Print Ovid

5 or/1-4
8 (multimicro-nutrient$ or multimicronutrient$).tw,kf.
13 (folic$ or folate$ or folvite$ or folacin$ or pteroylglutamic$).tw,kf. (2861)
17 ((fortif$ or supplement$) adj3 (cereal$ or condiment$ or flour$ or legume$ or rice$ or salt$ or sauce$ or milk$ or formula)).tw,kf.)
18 ("point of use" or point-of-use or "ready to use" or "ready -to- use" or RUSF$1 or RUTF$1 or FBF$1).tw,kf.
20 weaning.tw,kf.
23 or/6-22
24 5 and 23
33 or/25-32
34 24 and 33
Embase Ovid
1 exp anemia/
2 (anaem$ or anem$ or non-anemic$ or non-anaemic$).tw,kw.
3 (iron$ adj3 (deficien$ or status)).tw,kw.
4 (haemoglobin or hemoglobin or Hb).tw,kw.
5 (ferric or ferrous or ferritin$ or Fe).tw,kw. (138543)
6 or/1-5
7 exp diet therapy/
8 dietary supplement/
9 diet/
10 exp trace element/
11 functional food/
12 fortified food/
13 biofortification/
14 iron/
(Review)
Informed decisions.
15 zinc/
16 retinol/
18 (micronutrient$ or micro-nutrient$).tw,kw.
19 (multinutrient$ or multi-nutrient$ or multi$ nutrient$).tw,kw.
20 (multimicro-nutrient$ or multimicronutrient$).tw,kw.
21 (MNPs or MMPs or Sprinkles or Vita Shakti or Rahama or Anuka or Chispitas or BabyFer or Bebe Vanyan or Supplefer or Supplefem).tw,kw.
22 (multivitamin$ or multi-vitamin$).tw,kw.
23 (trace adj (element$ or mineral$ or nutrient$)).tw,kw.
24 iron intake/
25 iron chelating agent/
26 (iron$ or zinc$ or "vitamin A" or retinol$).tw,kw.
27 (folic$ or folate$ or folvite$ or folacin$ or pteroylglutamic$).tw,kw.
28 exp lipid/
29 (fatty acid$ or Docosahexaenoic acid$ or Eicosapentaenoic Acid$ or PUFA$ or lipid$ or omega 3$ or omega 6$).tw,kw.
30 (soy$ or wheat-soy$ or corn-soy$ or peanut or groundnut or whey or sesame or cashew or chickpea or oil$).tw,kw.
31 ((fortif$ or supplement$) adj3 (blend$ or diet$ or food$ or nutrition$)).tw,kw.
32 ((fortif$ or supplement$) adj3 (cereal$ or condiment$ or flour$ or legume$ or rice$ or salt$ or sauce$ or milk$ or formula)).tw,kw.
33 ("point of use" or point-of-use or "ready to use" or "ready -to- use" or RUSF$1 or RUTF$1 or FBF$1).tw,kw.
34 weaning/
35 weaning.tw,kw.
36 (complementary adj3 (feed$ or food$ or nutrition$)).tw,kw.
37 (biofortif$ or bio-fortif$).tw,kw.
38 or/7-37
39 6 and 38
40 nutritional science/
41 diet/
42 exp diet therapy/
43 nutrition/
44 or/40-43
45 health education/
46 health promotion/
47 counseling/
48 or/45-47
49 44 and 48
50 nutrition education/
51 nutritional counseling/ (2180)
52 ((nutrition$ or diet$ or food or feeding) adj3 (counsel$ or education$ or teach$ or class$)).tw,kw.
53 or/49-52
54 6 and 53
55 39 or 54
56 meta analysis/
57 "systematic review"/
65 ((inclusion or selection or predefined or pre-defined or predetermined or pre-determined) adj5 (studies or articles or reports)).ab.
66 or/56-65
67 55 and 66
68 exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/
69 human/ or normal human/ or human cell/
70 68 and 69
71 68 not 70
72 67 not 71
73 limit 72 to dc=20180701-20200824
(Review)
Informed decisions.
CINAHL Plus EBSCOhost (Cumulative Index to Nursing and Allied Health Literature)
S1 (MH "Anemia+")
S2 TI (anaem* or anem* or non-anemic* or non-anaemic*) OR AB (anaem* or anem* or non-anemic* or non-anaemic*)
S3 TI (iron* N3 (deficien* or status)) OR AB (iron* N3 (deficien* or status))
S4 TI (haemoglobin or hemoglobin or Hb) OR AB (haemoglobin or hemoglobin or HB
S5 TI (ferric or ferrous or ferritin* or Fe) OR AB (ferric or ferrous or ferritin* or Fe)
S6 S1 OR S2 OR S3 OR S4 OR S5
S7 (MH "Nutrition+")
S8 (MH "Dietary Supplements+") OR (MH "Food, Fortified") OR (MH "Food, Formulated") OR (MH "Food, Genetically Modified")
S9 (MH "Food/TU")
S10 (MH "Micronutrients")
S11 (MH "Diet")
S12 (MH "Biofortification")
S13 (MH "Iron") OR (MH "Iron Compounds")
S14 (MH "Zinc")
S15 (MH "Vitamin A")
S16 TI (nutrition* or diet*)
S17 TI (micronutrient* or micro-nutrient* OR micro nutrient*) OR AB (micronutrient* or micro-nutrient* OR micro nutrient*)
S18 TI(multinutrient* or multi-nutrient* or multi nutrient*" OR AB(multinutrient* or multi-nutrient* or multi nutrient*)
S19 TI (multimicro-nutrient* or multimicronutrient*) OR AB (multimicro-nutrient* or multimicronutrient*)
S20 TI (MNPs or MMPs or Sprinkles or Vita Shakti or Rahama or Anuka or Chispitas or BabyFer or Bebe Vanyan or Supplefer or Supplefem)
OR AB (MNPs or MMPs or Sprinkles or Vita Shakti or Rahama or Anuka or Chispitas or BabyFer or Bebe Vanyan or Supplefer or Supplefem)
S21 TI (multivitamin* or multi-vitamin* or multi vitamin*) OR AB (multivitamin* or multi-vitamin* or multi vitamin*)
S22 TI (trace N1 (element* or mineral*or nutrient*) OR AB (trace N1 (element* or mineral*or nutrient*)
S23 TI (iron* or zinc*or "vitamin A" or retinol*) OR AB (iron* or zinc*or "vitamin A" or retinol*)
S24 TI (folic* or folate* or folvite* or folacin* or pteroylglutamic*) OR AB(folic* or folate* or folvite* or folacin* or pteroylglutamic*)
S25 (MH "Lipids")
S26 TI (fatty acid* or Docosahexaenoic acid* or Eicosapentaenoic Acid* or PUFA* or lipid* or omega 3* or omega 6* OR omega- 3* OR
omega-6*) OR AB (fatty acid* or Docosahexaenoic acid* or Eicosapentaenoic Acid* or PUFA* or lipid* or omega 3* or omega 6* OR omega-
3* OR omega-6*)
S27 TI (soy* or wheat-soy* or corn-soy* or peanut or groundnut or whey or sesame or cashew or chickpea or oil*) OR AB (soy* or wheat-
soy* or corn-soy* or peanut or groundnut or whey or sesame or cashew or chickpea or oil*)
S28 TI ((fortif* or supplement*) N3 (blend* or diet* or food* or nutrition*) OR AB ((fortif* or supplement*) N3 (blend* or diet* or food* or
nutrition*)
S29 TI ((fortif* or supplement*) N3 (cereal* or condiment* or flour* or legume* or rice* or salt* or sauce* or milk* or formula)) OR AB((fortif*
or supplement*) N3 (cereal* or condiment* or flour* or legume* or rice* or salt* or sauce* or milk* or formula))
S30 TI ("point of use" or point-of-use or "ready to use" or "ready -to- use" or RUSF*1 or RUTF*1 or FBF*1) OR AB ("point of use" or point-
of-use or "ready to use" or "ready -to- use" or RUSF*1 or RUTF*1 or FBF*1)
S31 (MH "Weaning")
S32 TI (complementary N3 (feed* or food* or nutrition*) OR AB (complementary N3 (feed* or food* or nutrition*)
S33 TI(weaning) OR AB(weaning)
S34 TI(biofortif* or bio-fortif* OR AB (biofortif* or bio-fortif*)
S35 (MH "Diet Therapy")
S36 (MH "Health Promotion")
S37 (MH "Nutritional Counseling")
S38 (MH "Nutrition Education")
S39 TI ((nutrition* or diet* or food or feeding) N3 (counsel* or education* or teach* or class*)) OR AB ((nutrition* or diet* or food or feeding)
N3 (counsel* or education* or teach* or class*))
S40 S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR
S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39
S41 S6 AND S40
S42 (MH "Anemia, Iron Deficiency/DH/PC/TH")
S43 S41 OR S42
S44 (MH "Systematic Review")
S45 (MH "Meta Analysis")
S46 (MH "Meta Synthesis")
S47 TI (systematic* review*) OR AB (systematic* review*)
S48 TI (metanalysis or metaanalysis or meta analysis OR meta- analysis) OR AB (metanalysis or metaanalysis or meta analysis OR meta-
analysis)
S49 TI (metaregression or meta-regression or meta regression) OR AB (metaregression or meta-regression or meta regression)
S50 TI (metasynthesis or meta-synthesis or meta synthesis) OR AB (metasynthesis or meta-synthesis or meta synthesis)
(Review)
Informed decisions.
S51 (realist review or realist synthesis or rapid review or pragmatic review or umbrella review)
S52 AB (Medline or Pubmed or Embase or Cinahl or Cochrane)
S53 AB ((literature or database* or bibliographic) N3 search*)
S54 AB ((inclusion or selection or predefined or predetermined) N5 (studies or articles or reports))
S55 S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR S51 OR S52 OR S53 OR S54
S56 S43 AND S55
S57 EM 20180701-
S58 S56 AND S57
Database of Abstract of Reviews of Effects, in the Cochrane Library

#1 [mh anemia]
#2 (anaem* or anem* or non-anemic* or non-anaemic*):ti,ab
#3 (iron* near/3 (deficien* or status)):ti,ab
#4 (haemoglobin or hemoglobin or Hb):ti,ab
#5 (ferric or ferrous or ferritin* or Fe):ti,ab
#6 {or #1-#5} in Other Reviews
Epistemonikos (www.epistemonikos.org)
(title:((anem* OR anaem* OR non-anaem* OR non-anem* OR "iron defic*")) OR abstract:((anem* OR anaem* OR non-anaem* OR non-
anem* OR "iron defic*"))) AND (title:((supplement* OR complement* OR food OR feeding OR fortif* OR nutrient* OR micronutrient* OR
nutrition* OR MMN* OR RTUF OR RUSF OR iron* OR zinc OR "Vitamin A" OR educat* OR class* OR counsel*)) OR abstract:((supplement* OR
complement* OR food OR feeding OR fortif* OR nutrient* OR micronutrient* OR nutrition* OR MMN* OR RTUF OR RUSF OR iron* OR zinc
OR "Vitamin A" OR educat* OR class* OR counsel*)))
POPLINE (www.popline.org)
Taxonomy term IDs from the Keyword vocabulary:FOOD SUPPLEMENTATION OR Taxonomy
term IDs from the Keyword vocabulary:CHILD NUTRITION OR Taxonomy term IDs
from the Keyword vocabulary:INFANT NUTRITION OR Taxonomy term IDs from the
Keyword vocabulary:MATERNAL NUTRITION OR Taxonomy term IDs from the Keyword vocabulary:IRON OR Taxonomy term IDs from the Keyword
vocabulary:HEALTH EDUCATION OR Taxonomy term IDs from the Keyword vocabulary:EDUCATION
OR Taxonomy term IDs from the Keyword vocabulary:VITAMIN A OR Taxonomy term
IDs from the Keyword vocabulary:VITAMINS AND MINERALS OR Taxonomy term IDs from
the Keyword vocabulary:SUPPLEMENTARY FEEDING OR Taxonomy term IDs from the Keyword vocabulary:WEANING))) AND ((("meta analysis" OR "meta\-analysi"s OR "SYSTEMATIC REVIEW" OR
metaregression OR "meta\-regression" OR "meta regression" OR metasynthesis OR "meta\-synthesis" OR "meta synthesis")))
PROSPERO (www.crd.york.ac.uk/prospero)
#1 (iron deficien* OR iron status):CS
#2 (haemoglobin OR hemoglobin):CS
#3 (ferric OR ferrous OR ferritin OR Fe):CS
#4 (anaem* OR anem* OR non-anaem* OR non-anem*):CS
#5 #4 OR #3 OR #2 OR #1
#6 (diet* OR nutrition OR food* OR feed* OR supplement* OR micro* OR multi* OR biofortif* OR educat* OR teach* OR class*):IV
#7 #5 AND #6
#8 (diet* OR nutrition OR food* OR feed* OR supplement* OR micro* OR multi* OR biofortif* OR educat* OR teach* OR class*):IV WHERE
CD FROM 25/07/2018 TO 25/08/2020
#9 #5 AND #8
CS = condition studied
IV= intervention
Campbell Collaboration Online Library of Systematic Reviews (www.campbellcollaboration.org/better-evidence.html)

We conducted the following individual searches:
Title: Anaemia, Anemia, Iron, Supplementation, Fortification
Keywords: Anaemia, Anemia, Iron, Supplementation, Fortification
(Review)
Informed decisions.
3ie Database of Systematic Reviews (developmentevidence.3ieimpact.org/)

We limited the search to systematic reviews and individually searched for the following terms:
Anaemia, Anemia, Iron, Supplementation, Fortification
WHAT'S NEW
Date Event Description
7 January 2022 Amended Removing additional spaces that had been introduced into the
text of the review by a bug.
HISTORY
Protocol first published: Issue 8, 2018
Review first published: Issue 9, 2021
Date Event Description
20 August 2018 Amended Correcting Maria García-Casal's DOI. See Declarations of interest.
CONTRIBUTIONS OF AUTHORS
Maria N García-Casal (MNGC) contributed to the design of the review. Katharina da Silva Lopes (KL), Yo Takemoto (YT), and Erika Ota (EO)
drafted the protocol. KL, Noyuri Yamaji (NY), Md Obaidur Rahman (OR), Maiko Suto (MS), and YT extracted review characteristics and data,
and assessed the methodological quality of reviews independently. KL wrote the manuscript with the help of NY, OR, MS and EO. All authors
provided critical comments and valuable suggestions.
The contact author, Erika Ota, is the guarantor for the review.
DECLARATIONS OF INTEREST
Katharina da Silva Lopes: none known
Noyuri Yamaji: none known
Md Obaidur Rahman: none known
Maiko Suto: none known
Yo Takemoto: none known
Maria Nieves García-Casal (MNGC) is a full-time member of staff at the Department of Nutrition and Food Safety, World Health Organization
(WHO). MNGC declares no other known conflicts of interest.
Erika Ota's institution received funding (2017/725990) for this work from the Evidence and Programme Guidance, Department of Nutrition
for Health and Development, WHO, Switzerland.
EO, KL and MNGC are authors of included reviews (EO: Abe 2016, Rumbold 2015, Suchdev 2020; KL: Suchdev 2020; MNGC: Garcia-Casal
2018, Peña-Rosas 2015b, Peña-Rosas 2019). EO and MNGC were not involved in review selection, data extraction and assessment of
methodological quality using AMSTAR (Shea 2007a; Shea 2007b; Shea 2009). KL was involved in these tasks but not in relation to her own
reviews; in those cases, these tasks were performed by two other independent review authors (OR, NY).
Disclaimer: The review authors alone are responsible for the views expressed in this publication and they do not necessarily represent the
decisions, policy or views of the WHO.
(Review)
Informed decisions.
SOURCES OF SUPPORT
Internal sources
• Department of Nutrition and Food Safety, World Health Organization (WHO), Switzerland
Dr Maria Nieves García-Casal is a full-time member of staff at the WHO.
External sources
• Department of Nutrition and Food Safety, WHO, Switzerland
Provided financial support for the development of this overview of systematic reviews
• Bill & Melinda Gates Foundation, USA
The WHO gratefully acknowledges the financial contribution of the Bill & Melinda Gates Foundation towards the development of
overviews of systematic reviews of the evidence on the effects of nutrition interventions.
• MHLW Healthy Next Generation Program Grant Number JPMH20DA0601, Japan
This work was supported by MHLW Program Grant.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

Three additional authors joined the review team: Noyuri Yamaji, Maiko Suto, and Md. Obaidur Rahman.
We identified several reviews that included mixed populations (e.g. men and women), which we could not allocate to one of the
prespecified age groups. Therefore, we created a new category, 'mixed populations', as a type of participants.
We included reviews with other trial designs if the results for RCTs were reported separately.
We excluded reviews where our primary or secondary outcomes were not included or prespecified. This became necessary because
we already included a high number of systematic reviews. Including reviews without our primary or secondary outcomes would have
increased the number of included reviews dramatically, making our overview review confusing, unclear and difficult to convey to the reader
which interventions prevent or control anaemia.
We searched the final issue of DARE in 2018, after which no new content was added to this database. The POPLINE website was retired on
1 September 2019 so was no longer available for the top-up search.
We assessed risk of bias using AMSTAR (Shea 2007a; Shea 2007b; Shea 2009), however, we did not show the overall rating scores.
NOTES
Typo corrected in the abstract.
INDEX TERMS
Medical Subject Headings (MeSH)

*Anemia [epidemiology] [prevention & control]; *Anemia, Iron-Deficiency [epidemiology] [prevention & control]; Dietary
Supplements; Food, Fortified; Iron; Life Cycle Stages; Micronutrients; Systematic Reviews as Topic
MeSH check words

Adolescent; Adult; Aged; Animals; Child; Female; Humans; Male; Middle Aged; Pregnancy; Young Adult
(Review)

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Nutrition-specific interventions for preventing and controlling

Nutrition-specific interventions for preventing and controlling anaemia

Contact: Erika Ota, ota@slcn.ac.jp.

Editorial group: Cochrane Developmental, Psychosocial and Learning Problems Group.

Infants (6 to 23 months; 13 reviews)

Preschool and school-aged children (2 to 10 years; 8 reviews)

Adolescent children (11 to 18 years; 4 reviews)

Non-pregnant women of reproductive age (19 to 49 years; 5 reviews)

Pregnant women of reproductive age (15 to 49 years; 23 reviews)

Mixed population (all ages; 22 reviews)

PLAIN LANGUAGE SUMMARY

Interventions throughout life for the prevention or treatment of anaemia

What is the issue?

Why is this important?

What evidence did we find?

Preschool and school-aged children (2 to 10 years)

Adolescent children (11 to 18 years)

Non-pregnant women of reproductive age (19 to 49 years)

Pregnant women of reproductive age (15 to 49 years)

Mixed population (all ages)

What does this mean?

BACKGROUND respectively (WHO 2015). Anaemia prevalence decreased globally

were presented separately, we extracted data according to age Types of comparisons

Data synthesis RESULTS

Figure 1. Study flow diagram.

Adolescent children (aged 11 to 18 years)

high-certainty evidence). In one trial, the intervention showed no Prevention

Nutritional supplementation status selected by trialists, ID was measured by trial authors

MMN fortification versus no fortification Intravenous iron versus oral iron

Iron folic acid supplementation versus placebo Prevention

Vitamin A supplementation Thrity-one RCTs, cluster-RCTs and quasi-RCTs randomising 17,771

Fortification (2 reviews) Supplementation (9 reviews)

Prevention RCTs evaluated Hb concentrations for adolescents and adults

Iron with MMN versus placebo, no treatment, or iron supplementation Prevention

Fortification Improving dietary diversity and quality

De-Regil 2015 10.1002/14651858.CD010187.pub2] [PMC6517107] [PMID:

Petry 2016b Salam 2016

Pratt 2015 Salam 2020

Rumbold 2015 Suchdev 2015

Sultan 2019 and adults. Journal of Nutrition 2009;139(5):1022-30. [DOI:

2011;5(5):1280-5. [DOI: 10.5205/reuol.1302-9310-2- Fishman 2000

Iannotti 2006 2014;4(6):e004647. [DOI: 10.1136/bmjopen-2013-004647]

Martínez 2020 Milne 2009

deficiency and food fortification. Iranian Journal of Public Shao 2019

Additional references Baltussen 2004

Charles 2011 card/en/c/5aacbe39-068f-513b-b17d-1d92959654ea. [ISBN

prospero/display_ record.php?ID=CRD42018093744] Jackson 2005

Mason 2013 PAHO 2003

Moore 2014 Prentice 2017

Paganini 2017 Ruel 2003

Shea 2009 UN 2015

Siegfried 2012 UNICEF 1999

reviews of intervention effects on child survival. International WHO 2016a

Zandonadi 2017 Zimmermann 2007

Table 1. Unused methods

Table 2. Excluded reviews: reasons for exclusion

Table 2. Excluded reviews: reasons for exclusion (Continued)

Table 2. Excluded reviews: reasons for exclusion (Continued)

Table 2. Excluded reviews: reasons for exclusion (Continued)

Table 2. Excluded reviews: reasons for exclusion (Continued)

Cochrane Database of Systematic Reviews

Cochrane Database of Systematic Reviews

Cochrane Database of Systematic Reviews